本研究探討維生素B群、硫辛酸與牛磺酸等對小鼠腦微膠細胞株(microglia) BV-2吞噬及清除寡聚態類澱粉樣蛋白(oligomeric beta-amyloid, oAβ1-42)之影響，評估這些營養素是否能藉由降低過多的oAβ1-42堆積以延緩阿茲海默氏症之進展。
實驗首先建立體外小鼠微膠細胞株BV-2攝入oAβ1-42之細胞模式。將Aβ1-42粉末溶於F12 medium中24小時進行聚集反應以製備oAβ1-42。穿透式電子顯微鏡(transmission electron microscopy, TEM)型態觀察顯示所製備的oAβ1-42為聚集型球狀構造；以分析型超高速離心機(analytical ultracentrifugation, AUC)進行沉降係數分析，結果顯示製備的oAβ1-42分子量大多介於100-300 kDa之間。在細胞實驗方面，MTT分析結果發現，在0.1 mM的樣品濃度下測試樣品thiamin、riboflavin、nicotinamide、pyridoxine、cobalamin、folic acid、taurine、α-lipoic acid (ALA)對BV-2細胞皆無明顯之毒性產生。接著，以此樣品濃度處理經1 μM螢光分子標定的oAβ1-42 (FAM-oAβ1-42) 共培養24小時之小鼠微膠細胞株BV-2以進行攝入試驗，結果發現，在所有樣品中以ALA對BV-2細胞具有最佳的促進攝入FAM-oAβ1-42之效果。進一步以real-time PCR對microglia細胞表面上與oAβ吞噬作用相關之接受器(receptor)，包括scavenger receptor A1 (SR-A1)、scavenger receptor B1 (SR-B1)、CD36、receptor for advanced glycation end-products (RAGE)之基因表現進行分析。結果發現，與 oAβ1-42共同培養的BV-2細胞其CD36基因表現會隨著ALA處理濃度增加而升高，然而其他接受器則無；再則，以ALA處理未與oAβ1-42共同培養的BV-2細胞時也觀察到其CD36基因的表現有上升之情形。免疫細胞染色法(immunocytochemistry, ICC)結果顯示，無論是否與oAβ1-42共同培養，ALA的處理均會增加BV-2細胞CD36接受器之表現量，但添加CD36接受器阻斷劑(CD36抗體)則會顯著地減少ALA提升BV-2細胞對FAM-oAβ1-42之攝入能力。ICC分析結果亦發現，ALA處理會增加BV-2細胞中CD36的轉錄因子PPAR-γ (peroxisome proliferator-activated receptor-γ)之轉位作用(translocation)。Enzyme-linked immunosorbent assay (ELISA)分析發現，ALA處理會增加BV-2細胞對15-deoxy-△12,14- prostaglandin J2的產生。Real-time PCR以及western blotting分析結果發現，經ALA處理的BV-2細胞其COX-2基因與蛋白質之表現均有明顯增加之趨勢。根據上述結果，我們推測ALA可能是透過COX-2/15-deoxy-△12,14-prostaglandin J2/PPAR-γ/CD36路徑，提升BV-2細胞膜上CD36接受器之表現、增加其對oAβ1-42進行辨識，進而促進對oAβ1-42之吞噬作用。

The aim of this study is to investigate the effect of vitamin B complex (including thiamin, riboflavin, nicotinamide, pyridoxine, cobalamin, folic acid), vitamin-like α-lipoic acid (ALA), and taurine on enhancing phagocytosis of oAβ1-42 in BV-2 mouse microglia cells.
An in vitro model was established to investigate phagocytosis of oAβ1-42 in BV-2 mouse microglia cells. The image of transmission electron microscopy (TEM) indicated that the morphology of prepared oAβ1-42 was spherical particles. In addition, the data from analytical ultracentrifugation (AUC) showed that Aβ1-42 assembled by themselves to form oligomers with molecular size of 100-300 kDa principally. The MTT test revealed non-cytotoxicity of all tested compounds at concentration up to 100 μM on BV-2 cells. The BV-2 microglia cells were incubated with 1 μM 5(6)-carboxyfluorescein-labeled oAβ1-42 (FAM-oAβ1-42) for 24 h followed by flow cytometer analysis to assess the in vitro phagocytosis ability of oAβ1-42. The results showed that ALA exhibits the highest enhancing effect on phagocytosis of FAM-oAβ1-42 in BV-2 mouse microglia cells among all tested samples. Furthermore, the mRNA expressions of oAβ1-42 phagocytosis-related receptors of microglia were analyzed by real-time PCR for elucidating the phagocytosis mechanisms, and the results indicated that ALA significantly increases the mRNA expression of CD36 receptor in BV-2 cells. However, no significant difference was observed for other tested receptors, including scavenger receptor A1, scavenger receptor B1, and the receptor for advanced glycation end-products (RAGE). Interestingly, when treated with ALA alone, CD36 mRNA expression also increased in BV-2 cells even though without oAβ1-42 stimulation. The immunocytochemistry (ICC) analysis showed that ALA significantly elevated CD36 protein expression in BV-2 cells whether with or without oAβ1-42 treatment. Moreover, the results from flow cytometry analysis indicated CD36 receptor blocking antibody, the CD36 receptor inhibitor, significantly attenuated ALA-promoted phagocytosis of FAM-oAβ1-42 in BV-2 cells. The ICC analysis revealed that ALA caused translocation of PPAR-γ, which was known to regulate expression of CD36 mRNA, in BV-2 cells obviously. The real-time PCR and western blotting also revealed that ALA elevated both mRNA and protein expression of cyclooxygenase-2 (COX-2), a key enzyme that involved in the synthesis process of 15-deoxy-△12,14- prostaglandin J2, in BV-2 mouse micrgolia cells. Conclusively, we postulated that ALA enhances oAβ1-42 phagocytosis via up-regulation of COX-2/15-deoxy-△12,14-prostaglandin J2/PPAR-γ/CD36 pathway in BV-2 cells.

Aarum, J., Sandberg, K., Haeberlein, S. L., & Persson, M. A. (2003). Migration and differentiation of neural precursor cells can be directed by microglia. Proceedings of the National Academy of Sciences of the United States of America, 100(26), 15983-15988. doi: 10.1073/pnas.2237050100
Ahmadian, M., Suh, J. M., Hah, N., Liddle, C., Atkins, A. R., Downes, M., & Evans, R. M. (2013). PPARgamma signaling and metabolism: the good, the bad and the future. Nature medicine, 19(5), 557-566. doi: 10.1038/nm.3159
Aisen, P. S. (2002). The potential of anti-inflammatory drugs for the treatment of Alzheimer's disease. The Lancet. Neurology, 1(5), 279-284.
Alom, J., Mahy, J. N., Brandi, N., & Tolosa, E. (1991). Cerebrospinal fluid taurine in Alzheimer's disease. Annals of neurology, 30(5), 735. doi: 10.1002/ana.410300518
Arai, H., Kobayashi, K., Ichimiya, Y., Kosaka, K., & Iizuka, R. (1984). A preliminary study of free amino acids in the postmortem temporal cortex from Alzheimer-type dementia patients. Neurobiol Aging, 5(4), 319-321.
Ashoori, M., & Saedisomeolia, A. (2014). Riboflavin (vitamin B2) and oxidative stress: a review. The British journal of nutrition, 1-7. doi: 10.1017/s0007114514000178
Bard, F., Cannon, C., Barbour, R., Burke, R. L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Lieberburg, I., Motter, R., Nguyen, M., Soriano, F., Vasquez, N., Weiss, K., Welch, B., Seubert, P., Schenk, D., & Yednock, T. (2000). Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nature medicine, 6(8), 916-919. doi: 10.1038/78682
Bartzokis, G. (2011). Alzheimer's disease as homeostatic responses to age-related myelin breakdown. Neurobiol Aging, 32(8), 1341-1371. doi: 10.1016/j.neurobiolaging.2009.08.007
Bartzokis, G., Lu, P. H., & Mintz, J. (2004). Quantifying age-related myelin breakdown with MRI: novel therapeutic targets for preventing cognitive decline and Alzheimer's disease. Journal of Alzheimer's disease : JAD, 6(6 Suppl), S53-59.
Bartzokis, G., Lu, P. H., & Mintz, J. (2007). Human brain myelination and amyloid beta deposition in Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association, 3(2), 122-125. doi: 10.1016/j.jalz.2007.01.019
Bell, R. D., & Zlokovic, B. V. (2009). Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease. Acta neuropathologica, 118(1), 103-113. doi: 10.1007/s00401-009-0522-3
Benilova, I., Karran, E., & De Strooper, B. (2012). The toxic Abeta oligomer and Alzheimer's disease: an emperor in need of clothes. Nature neuroscience, 15(3), 349-357. doi: 10.1038/nn.3028
Bertram, L., & Tanzi, R. E. (2008). Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses. Nature reviews. Neuroscience, 9(10), 768-778. doi: 10.1038/nrn2494
Blasi, E., Barluzzi, R., Bocchini, V., Mazzolla, R., & Bistoni, F. (1990). Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus. Journal of neuroimmunology, 27(2-3), 229-237.
Blennow, K. (2004). Cerebrospinal fluid protein biomarkers for Alzheimer's disease. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics, 1(2), 213-225. doi: 10.1602/neurorx.1.2.213
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006). Alzheimer's disease. The Lancet, 368(9533), 387-403. doi: 10.1016/s0140-6736(06)69113-7
Blennow, K., & Hampel, H. (2003). CSF markers for incipient Alzheimer's disease. The Lancet. Neurology, 2(10), 605-613.
Block, M. L., Zecca, L., & Hong, J. S. (2007). Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nature reviews. Neuroscience, 8(1), 57-69. doi: 10.1038/nrn2038
Brookmeyer, R., Johnson, E., Ziegler-Graham, K., & Arrighi, H. M. (2007). Forecasting the global burden of Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association, 3(3), 186-191. doi: 10.1016/j.jalz.2007.04.381
Bruni, A. C. (1998). Cloning of a gene bearing missense mutations in early onset familial Alzheimer's disease: a Calabrian study. Functional neurology, 13(3), 257-261.
Bujold, K., Rhainds, D., Jossart, C., Febbraio, M., Marleau, S., & Ong, H. (2009). CD36-mediated cholesterol efflux is associated with PPARgamma activation via a MAPK-dependent COX-2 pathway in macrophages. Cardiovascular research, 83(3), 457-464. doi: 10.1093/cvr/cvp118
Butterworth, R. F., Giguere, J. F., & Besnard, A. M. (1985). Activities of thiamine-dependent enzymes in two experimental models of thiamine-deficiency encephalopathy: 1. The pyruvate dehydrogenase complex. Neurochemical research, 10(10), 1417-1428.
Butterworth, R. F., Giguere, J. F., & Besnard, A. M. (1986). Activities of thiamine-dependent enzymes in two experimental models of thiamine-deficiency encephalopathy. 2. alpha-Ketoglutarate dehydrogenase. Neurochemical research, 11(4), 567-577.
Cai, Z., Hussain, M. D., & Yan, L. J. (2014). Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer's disease. The International journal of neuroscience, 124(5), 307-321. doi: 10.3109/00207454.2013.833510
Calingasan, N. Y., Gandy, S. E., Baker, H., Sheu, K. F., Kim, K. S., Wisniewski, H. M., & Gibson, G. E. (1995). Accumulation of amyloid precursor protein-like immunoreactivity in rat brain in response to thiamine deficiency. Brain research, 677(1), 50-60.
Calingasan, N. Y., Gandy, S. E., Baker, H., Sheu, K. F., Smith, J. D., Lamb, B. T., Gearhart, J. D., Buxbaum, J. D., Harper, C., Selkoe, D. J., Price, D. L., Sisodia, S. S., & Gibson, G. E. (1996). Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency. The American journal of pathology, 149(3), 1063-1071.
Chawla, A., Barak, Y., Nagy, L., Liao, D., Tontonoz, P., & Evans, R. M. (2001). PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nature medicine, 7(1), 48-52. doi: 10.1038/83336
Chromy, B. A., Nowak, R. J., Lambert, M. P., Viola, K. L., Chang, L., Velasco, P. T., Jones, B. W., Fernandez, S. J., Lacor, P. N., Horowitz, P., Finch, C. E., Krafft, G. A., & Klein, W. L. (2003). Self-assembly of Abeta(1-42) into globular neurotoxins. Biochemistry, 42(44), 12749-12760. doi: 10.1021/bi030029q
Clarke, R., Smith, A. D., Jobst, K. A., Refsum, H., Sutton, L., & Ueland, P. M. (1998). Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Archives of neurology, 55(11), 1449-1455.
Crum, R. M., Anthony, J. C., Bassett, S. S., & Folstein, M. F. (1993). Population-based norms for the Mini-Mental State Examination by age and educational level. Jama, 269(18), 2386-2391.
Dahlgren, K. N., Manelli, A. M., Stine, W. B., Jr., Baker, L. K., Krafft, G. A., & LaDu, M. J. (2002). Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability. The Journal of biological chemistry, 277(35), 32046-32053. doi: 10.1074/jbc.M201750200
de Leon, M. J., McRae, T., Tsai, J. R., George, A. E., Marcus, D. L., Freedman, M., Wolf, A. P., & McEwen, B. (1988). Abnormal cortisol response in Alzheimer's disease linked to hippocampal atrophy. Lancet, 2(8607), 391-392.
Deane, R., Sagare, A., Hamm, K., Parisi, M., Lane, S., Finn, M. B., Holtzman, D. M., & Zlokovic, B. V. (2008). apoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain. The Journal of clinical investigation, 118(12), 4002-4013. doi: 10.1172/jci36663
Deane, R., Sagare, A., & Zlokovic, B. V. (2008). The role of the cell surface LRP and soluble LRP in blood-brain barrier Abeta clearance in Alzheimer's disease. Current pharmaceutical design, 14(16), 1601-1605.
Deane, R., Wu, Z., Sagare, A., Davis, J., Du Yan, S., Hamm, K., Xu, F., Parisi, M., LaRue, B., Hu, H. W., Spijkers, P., Guo, H., Song, X., Lenting, P. J., Van Nostrand, W. E., & Zlokovic, B. V. (2004). LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron, 43(3), 333-344. doi: 10.1016/j.neuron.2004.07.017
Douaud, G., Refsum, H., de Jager, C. A., Jacoby, R., Nichols, T. E., Smith, S. M., & Smith, A. D. (2013). Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment. Proceedings of the National Academy of Sciences of the United States of America, 110(23), 9523-9528. doi: 10.1073/pnas.1301816110
Eikelenboom, P., Rozemuller, J. M., & van Muiswinkel, F. L. (1998). Inflammation and Alzheimer's disease: relationships between pathogenic mechanisms and clinical expression. Experimental neurology, 154(1), 89-98. doi: 10.1006/exnr.1998.6920
El Khoury, J., Hickman, S. E., Thomas, C. A., Loike, J. D., & Silverstein, S. C. (1998). Microglia, scavenger receptors, and the pathogenesis of Alzheimer's disease. Neurobiol Aging, 19(1 Suppl), S81-84.
El Khoury, J., Toft, M., Hickman, S. E., Means, T. K., Terada, K., Geula, C., & Luster, A. D. (2007). Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nature medicine, 13(4), 432-438. doi: 10.1038/nm1555
Engelhart, M. J., Geerlings, M. I., Ruitenberg, A., van Swieten, J. C., Hofman, A., Witteman, J. C., & Breteler, M. M. (2002). Dietary intake of antioxidants and risk of Alzheimer disease. Jama, 287(24), 3223-3229.
Farr, S. A., Price, T. O., Banks, W. A., Ercal, N., & Morley, J. E. (2012). Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice. Journal of Alzheimer's disease : JAD, 32(2), 447-455. doi: 10.3233/jad-2012-120130
Farrer, L. A., Cupples, L. A., Haines, J. L., Hyman, B., Kukull, W. A., Mayeux, R., Myers, R. H., Pericak-Vance, M. A., Risch, N., & van Duijn, C. M. (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. Jama, 278(16), 1349-1356.
Feige, J. N., Gelman, L., Michalik, L., Desvergne, B., & Wahli, W. (2006). From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Progress in lipid research, 45(2), 120-159. doi: 10.1016/j.plipres.2005.12.002
Feng, Y., Li, L., & Sun, X. H. (2011). Monocytes and Alzheimer's disease. Neuroscience bulletin, 27(2), 115-122. doi: 10.1007/s12264-011-1205-3
Ferrer, I., Gomez-Isla, T., Puig, B., Freixes, M., Ribe, E., Dalfo, E., & Avila, J. (2005). Current advances on different kinases involved in tau phosphorylation, and implications in Alzheimer's disease and tauopathies. Current Alzheimer research, 2(1), 3-18.
Foley, D. J., & White, L. R. (2002). Dietary intake of antioxidants and risk of Alzheimer disease: food for thought. Jama, 287(24), 3261-3263.
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. Journal of psychiatric research, 12(3), 189-198.
Francis, P. T., Palmer, A. M., Snape, M., & Wilcock, G. K. (1999). The cholinergic hypothesis of Alzheimer's disease: a review of progress. Journal of neurology, neurosurgery, and psychiatry, 66(2), 137-147.
Gibson, C. J., Hossain, M. M., Richardson, J. R., & Aleksunes, L. M. (2012). Inflammatory regulation of ATP binding cassette efflux transporter expression and function in microglia. The Journal of pharmacology and experimental therapeutics, 343(3), 650-660. doi: 10.1124/jpet.112.196543
Gibson, G., Barclay, L., & Blass, J. (1982). The role of the cholinergic system in thiamin deficiency. Annals of the New York Academy of Sciences, 378, 382-403.
Gibson, G. E., Ksiezak-Reding, H., Sheu, K. F., Mykytyn, V., & Blass, J. P. (1984). Correlation of enzymatic, metabolic, and behavioral deficits in thiamin deficiency and its reversal. Neurochemical research, 9(6), 803-814.
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010). Mechanisms underlying inflammation in neurodegeneration. Cell, 140(6), 918-934. doi: 10.1016/j.cell.2010.02.016
Glezer, I., Simard, A. R., & Rivest, S. (2007). Neuroprotective role of the innate immune system by microglia. Neuroscience, 147(4), 867-883. doi: 10.1016/j.neuroscience.2007.02.055
Goate, A., Chartier-Harlin, M. C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., & et al. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature, 349(6311), 704-706. doi: 10.1038/349704a0
Goedert, M., Spillantini, M. G., & Crowther, R. A. (1991). Tau proteins and neurofibrillary degeneration. Brain pathology (Zurich, Switzerland), 1(4), 279-286.
Golbidi, S., Badran, M., & Laher, I. (2011). Diabetes and alpha lipoic Acid. Frontiers in pharmacology, 2, 69. doi: 10.3389/fphar.2011.00069
Gong, C. X., & Iqbal, K. (2008). Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Current medicinal chemistry, 15(23), 2321-2328.
Gotz, J., Eckert, A., Matamales, M., Ittner, L. M., & Liu, X. (2011). Modes of Abeta toxicity in Alzheimer's disease. Cellular and molecular life sciences : CMLS, 68(20), 3359-3375. doi: 10.1007/s00018-011-0750-2
Graeber, M. B., & Streit, W. J. (2010). Microglia: biology and pathology. Acta neuropathologica, 119(1), 89-105. doi: 10.1007/s00401-009-0622-0
Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1986). Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proceedings of the National Academy of Sciences of the United States of America, 83(13), 4913-4917.
Grygiel-Gorniak, B. (2014). Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications--a review. Nutrition journal, 13, 17. doi: 10.1186/1475-2891-13-17
Guidotti, A., Badiani, G., & Pepeu, G. (1972). Taurine distribution in cat brain. Journal of neurochemistry, 19(2), 431-435.
Haan, M. N. (2006). Therapy Insight: type 2 diabetes mellitus and the risk of late-onset Alzheimer's disease. Nature clinical practice. Neurology, 2(3), 159-166. doi: 10.1038/ncpneuro0124
Haass, C., & Selkoe, D. J. (2007). Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nature reviews. Molecular cell biology, 8(2), 101-112. doi: 10.1038/nrm2101
Hager, K., Kenklies, M., McAfoose, J., Engel, J., & Munch, G. (2007). Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis. Journal of neural transmission. Supplementum(72), 189-193.
Harvey, R. J., Skelton-Robinson, M., & Rossor, M. N. (2003). The prevalence and causes of dementia in people under the age of 65 years. Journal of neurology, neurosurgery, and psychiatry, 74(9), 1206-1209.
Heneka, M. T., Nadrigny, F., Regen, T., Martinez-Hernandez, A., Dumitrescu-Ozimek, L., Terwel, D., Jardanhazi-Kurutz, D., Walter, J., Kirchhoff, F., Hanisch, U. K., & Kummer, M. P. (2010). Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine. Proceedings of the National Academy of Sciences of the United States of America, 107(13), 6058-6063. doi: 10.1073/pnas.0909586107
Hickman, S. E., Allison, E. K., & El Khoury, J. (2008). Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice. The Journal of neuroscience : the official journal of the Society for Neuroscience, 28(33), 8354-8360. doi: 10.1523/jneurosci.0616-08.2008
Holmquist, L., Stuchbury, G., Berbaum, K., Muscat, S., Young, S., Hager, K., Engel, J., & Munch, G. (2007). Lipoic acid as a novel treatment for Alzheimer's disease and related dementias. Pharmacology & therapeutics, 113(1), 154-164. doi: 10.1016/j.pharmthera.2006.07.001
Holtta, M., Hansson, O., Andreasson, U., Hertze, J., Minthon, L., Nagga, K., Andreasen, N., Zetterberg, H., & Blennow, K. (2013). Evaluating amyloid-beta oligomers in cerebrospinal fluid as a biomarker for Alzheimer's disease. PloS one, 8(6), e66381. doi: 10.1371/journal.pone.0066381
Huang, Y., & Mucke, L. (2012). Alzheimer mechanisms and therapeutic strategies. Cell, 148(6), 1204-1222. doi: 10.1016/j.cell.2012.02.040
Huxtable, R. J. (1992). Physiological actions of taurine. Physiological reviews, 72(1), 101-163.
Hwang, J. S., An, J. M., Cho, H., Lee, S. H., Park, J. H., & Han, I. O. (2015). A dopamine-alpha-lipoic acid hybridization compound and its acetylated form inhibit LPS-mediated inflammation. European journal of pharmacology, 746, 41-49. doi: 10.1016/j.ejphar.2014.10.052
Iqbal, K., Alonso Adel, C., Chen, S., Chohan, M. O., El-Akkad, E., Gong, C. X., Khatoon, S., Li, B., Liu, F., Rahman, A., Tanimukai, H., & Grundke-Iqbal, I. (2005). Tau pathology in Alzheimer disease and other tauopathies. Biochimica et biophysica acta, 1739(2-3), 198-210. doi: 10.1016/j.bbadis.2004.09.008
Jellinger, K. A. (2004). Head injury and dementia. Current opinion in neurology, 17(6), 719-723.
Justice, E., & Carruthers, D. M. (2005). Cardiovascular risk and COX-2 inhibition in rheumatological practice. Journal of human hypertension, 19(1), 1-5. doi: 10.1038/sj.jhh.1001777
Kalinski, P. (2012). Regulation of immune responses by prostaglandin E2. Journal of immunology (Baltimore, Md. : 1950), 188(1), 21-28. doi: 10.4049/jimmunol.1101029
Kamenova, P. (2006). Improvement of insulin sensitivity in patients with type 2 diabetes mellitus after oral administration of alpha-lipoic acid. Hormones (Athens, Greece), 5(4), 251-258.
Kastenholz, B., Garfin, D. E., Horst, J., & Nagel, K. A. (2009). Plant metal chaperones: a novel perspective in dementia therapy. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 16(2), 81-83. doi: 10.1080/13506120902879392
Kawahara, K., Suenobu, M., Yoshida, A., Koga, K., Hyodo, A., Ohtsuka, H., Kuniyasu, A., Tamamaki, N., Sugimoto, Y., & Nakayama, H. (2012). Intracerebral microinjection of interleukin-4/interleukin-13 reduces beta-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice. Neuroscience, 207, 243-260. doi: 10.1016/j.neuroscience.2012.01.049
Kettenmann, H., Hanisch, U. K., Noda, M., & Verkhratsky, A. (2011). Physiology of microglia. Physiological reviews, 91(2), 461-553. doi: 10.1152/physrev.00011.2010
Kim, H. Y., Kim, H. V., Yoon, J. H., Kang, B. R., Cho, S. M., Lee, S., Kim, J. Y., Kim, J. W., Cho, Y., Woo, J., & Kim, Y. (2014). Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease. Scientific reports, 4, 7467. doi: 10.1038/srep07467
Koriyama, Y., Nakayama, Y., Matsugo, S., Sugitani, K., Ogai, K., Takadera, T., & Kato, S. (2013). Anti-inflammatory effects of lipoic acid through inhibition of GSK-3beta in lipopolysaccharide-induced BV-2 microglial cells. Neuroscience research, 77(1-2), 87-96. doi: 10.1016/j.neures.2013.07.001
LaFerla, F. M., Green, K. N., & Oddo, S. (2007). Intracellular amyloid-beta in Alzheimer's disease. Nature reviews. Neuroscience, 8(7), 499-509. doi: 10.1038/nrn2168
Lauren, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., & Strittmatter, S. M. (2009). Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature, 457(7233), 1128-1132. doi: 10.1038/nature07761
Lawson, L. J., Perry, V. H., & Gordon, S. (1992). Turnover of resident microglia in the normal adult mouse brain. Neuroscience, 48(2), 405-415.
Leissring, M. A., Farris, W., Chang, A. Y., Walsh, D. M., Wu, X., Sun, X., Frosch, M. P., & Selkoe, D. J. (2003). Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron, 40(6), 1087-1093.
Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, W. H., Yu, C. E., Jondro, P. D., Schmidt, S. D., Wang, K., & et al. (1995). Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science (New York, N.Y.), 269(5226), 973-977.
Liu, F., Grundke-Iqbal, I., Iqbal, K., & Gong, C. X. (2005). Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. The European journal of neuroscience, 22(8), 1942-1950. doi: 10.1111/j.1460-9568.2005.04391.x
Liu, Y., Zhang, R., Yan, K., Chen, F., Huang, W., Lv, B., Sun, C., Xu, L., Li, F., & Jiang, X. (2014). Mesenchymal stem cells inhibit lipopolysaccharide-induced inflammatory responses of BV2 microglial cells through TSG-6. Journal of neuroinflammation, 11, 135. doi: 10.1186/1742-2094-11-135
Lu'o'ng, K., & Nguyen, L. T. (2011). Role of thiamine in Alzheimer's disease. American journal of Alzheimer's disease and other dementias, 26(8), 588-598. doi: 10.1177/1533317511432736
Lu, D. Y., Tang, C. H., Liou, H. C., Teng, C. M., Jeng, K. C., Kuo, S. C., Lee, F. Y., & Fu, W. M. (2007). YC-1 attenuates LPS-induced proinflammatory responses and activation of nuclear factor-kappaB in microglia. British journal of pharmacology, 151(3), 396-405. doi: 10.1038/sj.bjp.0707187
Luchsinger, J. A., & Mayeux, R. (2004). Dietary factors and Alzheimer's disease. The Lancet. Neurology, 3(10), 579-587. doi: 10.1016/s1474-4422(04)00878-6
Luchsinger, J. A., Tang, M. X., Miller, J., Green, R., & Mayeux, R. (2007). Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Archives of neurology, 64(1), 86-92. doi: 10.1001/archneur.64.1.86
Luque-Contreras, D., Carvajal, K., & Toral-Rios, D. (2014). Oxidative stress and metabolic syndrome: cause or consequence of Alzheimer's disease? , 2014, 497802. doi: 10.1155/2014/497802
Maczurek, A., Hager, K., Kenklies, M., Sharman, M., Martins, R., Engel, J., Carlson, D. A., & Munch, G. (2008). Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer's disease. Advanced drug delivery reviews, 60(13-14), 1463-1470. doi: 10.1016/j.addr.2008.04.015
Maiese, K., & Chong, Z. Z. (2003). Nicotinamide: necessary nutrient emerges as a novel cytoprotectant for the brain. Trends in pharmacological sciences, 24(5), 228-232. doi: 10.1016/s0165-6147(03)00078-6
Marcinkiewicz, J., & Kontny, E. (2014). Taurine and inflammatory diseases. Amino acids, 46(1), 7-20. doi: 10.1007/s00726-012-1361-4
Medina, M., & Avila, J. (2014). New perspectives on the role of tau in Alzheimer's disease. Implications for therapy. Biochemical pharmacology, 88(4), 540-547. doi: 10.1016/j.bcp.2014.01.013
Miners, J. S., Morris, S., Love, S., & Kehoe, P. G. (2011). Accumulation of insoluble amyloid-beta in down's syndrome is associated with increased BACE-1 and neprilysin activities. Journal of Alzheimer's disease : JAD, 23(1), 101-108. doi: 10.3233/jad-2010-101395
Moga, T., & Das, S. (2013). The 2-Series Eicosanoids in Cancer: Future Targets for Glioma Therapy? Journal of Cancer Therapy, 04(01), 338-352. doi: 10.4236/jct.2013.41041
Molina, J. A., Jimenez-Jimenez, F. J., Hernanz, A., Fernandez-Vivancos, E., Medina, S., de Bustos, F., Gomez-Escalonilla, C., & Sayed, Y. (2002). Cerebrospinal fluid levels of thiamine in patients with Alzheimer's disease. Journal of neural transmission, 109(7-8), 1035-1044. doi: 10.1007/s007020200087
Morris, M. C., Evans, D. A., Bienias, J. L., Tangney, C. C., Bennett, D. A., Aggarwal, N., Wilson, R. S., & Scherr, P. A. (2002). Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. Jama, 287(24), 3230-3237.
Mungas, D. (1991). In-office mental status testing: a practical guide. Geriatrics, 46(7), 54-58, 63, 66.
Nardone, R., Holler, Y., Storti, M., Christova, M., Tezzon, F., Golaszewski, S., Trinka, E., & Brigo, F. (2013). Thiamine deficiency induced neurochemical, neuroanatomical, and neuropsychological alterations: a reappraisal. TheScientificWorldJournal, 2013, 309143. doi: 10.1155/2013/309143
Olmsted, J. B. (1986). Microtubule-associated proteins. Annual review of cell biology, 2, 421-457. doi: 10.1146/annurev.cb.02.110186.002225
Packer, L., Witt, E. H., & Tritschler, H. J. (1995). alpha-Lipoic acid as a biological antioxidant. Free radical biology & medicine, 19(2), 227-250.
Pan, X., Gong, N., Zhao, J., Yu, Z., Gu, F., Chen, J., Sun, X., Zhao, L., Yu, M., Xu, Z., Dong, W., Qin, Y., Fei, G., Zhong, C., & Xu, T. L. (2010). Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. Brain : a journal of neurology, 133(Pt 5), 1342-1351. doi: 10.1093/brain/awq069
Parkhurst, C. N., Yang, G., Ninan, I., Savas, J. N., Yates, J. R., 3rd, Lafaille, J. J., Hempstead, B. L., Littman, D. R., & Gan, W. B. (2013). Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell, 155(7), 1596-1609. doi: 10.1016/j.cell.2013.11.030
Patterson, C., Feightner, J. W., Garcia, A., Hsiung, G. Y., MacKnight, C., & Sadovnick, A. D. (2008). Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 178(5), 548-556. doi: 10.1503/cmaj.070796
Permanne, B., Adessi, C., Saborio, G. P., Fraga, S., Frossard, M. J., Van Dorpe, J., Dewachter, I., Banks, W. A., Van Leuven, F., & Soto, C. (2002). Reduction of amyloid load and cerebral damage in a transgenic mouse model of Alzheimer's disease by treatment with a beta-sheet breaker peptide. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 16(8), 860-862. doi: 10.1096/fj.01-0841fje
Perra, A., Pibiri, M., Sulas, P., Simbula, G., Ledda-Columbano, G. M., & Columbano, A. (2008). Alpha-lipoic acid promotes the growth of rat hepatic pre-neoplastic lesions in the choline-deficient model. Carcinogenesis, 29(1), 161-168. doi: 10.1093/carcin/bgm205
Petersen, R. C., Thomas, R. G., Grundman, M., Bennett, D., Doody, R., Ferris, S., Galasko, D., Jin, S., Kaye, J., Levey, A., Pfeiffer, E., Sano, M., van Dyck, C. H., & Thal, L. J. (2005). Vitamin E and donepezil for the treatment of mild cognitive impairment. The New England journal of medicine, 352(23), 2379-2388. doi: 10.1056/NEJMoa050151
Petit, A., Bihel, F., Alves da Costa, C., Pourquie, O., Checler, F., & Kraus, J. L. (2001). New protease inhibitors prevent gamma-secretase-mediated production of Abeta40/42 without affecting Notch cleavage. Nature cell biology, 3(5), 507-511. doi: 10.1038/35074581
Pohanka, M. (2013). Alzheimer s disease and oxidative stress: a review. Current medicinal chemistry, 21(3), 356-364.
Preston, S. D., Steart, P. V., Wilkinson, A., Nicoll, J. A., & Weller, R. O. (2003). Capillary and arterial cerebral amyloid angiopathy in Alzheimer's disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Neuropathology and applied neurobiology, 29(2), 106-117.
Prokop, S., Miller, K. R., & Heppner, F. L. (2013). Microglia actions in Alzheimer's disease. Acta neuropathologica. doi: 10.1007/s00401-013-1182-x
Qiu, W. Q., Walsh, D. M., Ye, Z., Vekrellis, K., Zhang, J., Podlisny, M. B., Rosner, M. R., Safavi, A., Hersh, L. B., & Selkoe, D. J. (1998). Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation. The Journal of biological chemistry, 273(49), 32730-32738.
Querfurth, H. W., & LaFerla, F. M. (2010). Alzheimer's disease. The New England journal of medicine, 362(4), 329-344. doi: 10.1056/NEJMra0909142
Ramer, R., Heinemann, K., Merkord, J., Rohde, H., Salamon, A., Linnebacher, M., & Hinz, B. (2013). COX-2 and PPAR-gamma confer cannabidiol-induced apoptosis of human lung cancer cells. Molecular cancer therapeutics, 12(1), 69-82. doi: 10.1158/1535-7163.mct-12-0335
Reddy, P. H., & Beal, M. F. (2008). Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends in molecular medicine, 14(2), 45-53. doi: 10.1016/j.molmed.2007.12.002
Rosendorff, C., Beeri, M. S., & Silverman, J. M. (2007). Cardiovascular risk factors for Alzheimer's disease. The American journal of geriatric cardiology, 16(3), 143-149.
Roychaudhuri, R., Yang, M., Hoshi, M. M., & Teplow, D. B. (2009). Amyloid beta-protein assembly and Alzheimer disease. The Journal of biological chemistry, 284(8), 4749-4753. doi: 10.1074/jbc.R800036200
Rubio-Perez, J. M., & Morillas-Ruiz, J. M. (2012). A review: inflammatory process in Alzheimer's disease, role of cytokines. TheScientificWorldJournal, 2012, 756357. doi: 10.1100/2012/756357
Sadowski, M., Pankiewicz, J., Scholtzova, H., Ripellino, J. A., Li, Y., Schmidt, S. D., Mathews, P. M., Fryer, J. D., Holtzman, D. M., Sigurdsson, E. M., & Wisniewski, T. (2004). A synthetic peptide blocking the apolipoprotein E/beta-amyloid binding mitigates beta-amyloid toxicity and fibril formation in vitro and reduces beta-amyloid plaques in transgenic mice. The American journal of pathology, 165(3), 937-948.
Santa-Maria, I., Hernandez, F., Moreno, F. J., & Avila, J. (2007). Taurine, an inducer for tau polymerization and a weak inhibitor for amyloid-beta-peptide aggregation. Neuroscience letters, 429(2-3), 91-94. doi: 10.1016/j.neulet.2007.09.068
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Liao, Z., Lieberburg, I., Motter, R., Mutter, L., Soriano, F., Shopp, G., Vasquez, N., Vandevert, C., Walker, S., Wogulis, M., Yednock, T., Games, D., & Seubert, P. (1999). Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature, 400(6740), 173-177. doi: 10.1038/22124
Schenk, D., Hagen, M., & Seubert, P. (2004). Current progress in beta-amyloid immunotherapy. Current opinion in immunology, 16(5), 599-606. doi: 10.1016/j.coi.2004.07.012
Scher, J. U., & Pillinger, M. H. (2005). 15d-PGJ2: the anti-inflammatory prostaglandin? Clinical immunology (Orlando, Fla.), 114(2), 100-109. doi: 10.1016/j.clim.2004.09.008
Seab, J. P., Jagust, W. J., Wong, S. T., Roos, M. S., Reed, B. R., & Budinger, T. F. (1988). Quantitative NMR measurements of hippocampal atrophy in Alzheimer's disease. Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, 8(2), 200-208.
Selkoe, D. J. (2008). Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behavioural brain research, 192(1), 106-113. doi: 10.1016/j.bbr.2008.02.016
Seshadri, S., Beiser, A., Selhub, J., Jacques, P. F., Rosenberg, I. H., D'Agostino, R. B., Wilson, P. W., & Wolf, P. A. (2002). Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. The New England journal of medicine, 346(7), 476-483. doi: 10.1056/NEJMoa011613
Shay, K. P., Moreau, R. F., Smith, E. J., Smith, A. R., & Hagen, T. M. (2009). Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochimica et biophysica acta, 1790(10), 1149-1160. doi: 10.1016/j.bbagen.2009.07.026
Sheng, W., Zong, Y., Mohammad, A., Ajit, D., Cui, J., Han, D., Hamilton, J. L., Simonyi, A., Sun, A. Y., Gu, Z., Hong, J. S., Weisman, G. A., & Sun, G. Y. (2011). Pro-inflammatory cytokines and lipopolysaccharide induce changes in cell morphology, and upregulation of ERK1/2, iNOS and sPLA(2)-IIA expression in astrocytes and microglia. Journal of neuroinflammation, 8, 121. doi: 10.1186/1742-2094-8-121
Shibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., & Zlokovic, B. V. (2000). Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. The Journal of clinical investigation, 106(12), 1489-1499. doi: 10.1172/jci10498
Shimizu, E., Kawahara, K., Kajizono, M., Sawada, M., & Nakayama, H. (2008). IL-4-induced selective clearance of oligomeric beta-amyloid peptide(1-42) by rat primary type 2 microglia. Journal of immunology (Baltimore, Md. : 1950), 181(9), 6503-6513.
Siemers, E., Skinner, M., Dean, R. A., Gonzales, C., Satterwhite, J., Farlow, M., Ness, D., & May, P. C. (2005). Safety, tolerability, and changes in amyloid beta concentrations after administration of a gamma-secretase inhibitor in volunteers. Clinical neuropharmacology, 28(3), 126-132.
Sokolowski, J. D., & Mandell, J. W. (2011). Phagocytic clearance in neurodegeneration. The American journal of pathology, 178(4), 1416-1428. doi: 10.1016/j.ajpath.2010.12.051
Steen, E., Terry, B. M., Rivera, E. J., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? Journal of Alzheimer's disease : JAD, 7(1), 63-80.
Su, B., Wang, X., Nunomura, A., Moreira, P. I., Lee, H. G., Perry, G., Smith, M. A., & Zhu, X. (2008). Oxidative stress signaling in Alzheimer's disease. Current Alzheimer research, 5(6), 525-532.
Sun, Q., Hu, H., Wang, W., Jin, H., Feng, G., & Jia, N. (2014). Taurine attenuates amyloid beta 1-42-induced mitochondrial dysfunction by activating of SIRT1 in SK-N-SH cells. Biochemical and biophysical research communications, 447(3), 485-489. doi: 10.1016/j.bbrc.2014.04.019
Terry, A. V., Jr., & Buccafusco, J. J. (2003). The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. The Journal of pharmacology and experimental therapeutics, 306(3), 821-827. doi: 10.1124/jpet.102.041616
Thirunavukkarasu, V., Anitha Nandhini, A. T., & Anuradha, C. V. (2004). Lipoic acid attenuates hypertension and improves insulin sensitivity, kallikrein activity and nitrite levels in high fructose-fed rats. Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology, 174(8), 587-592. doi: 10.1007/s00360-004-0447-z
Tontonoz, P., Nagy, L., Alvarez, J. G., Thomazy, V. A., & Evans, R. M. (1998). PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell, 93(2), 241-252.
Turunc Bayrakdar, E., Uyanikgil, Y., Kanit, L., Koylu, E., & Yalcin, A. (2014). Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Abeta(1-42)-induced rat model of Alzheimer's disease. Free radical research, 48(2), 146-158. doi: 10.3109/10715762.2013.857018
Ulivi, V., Lenti, M., Gentili, C., Marcolongo, G., Cancedda, R., & Descalzi Cancedda, F. (2011). Anti-inflammatory activity of monogalactosyldiacylglycerol in human articular cartilage in vitro: activation of an anti-inflammatory cyclooxygenase-2 (COX-2) pathway. Arthritis research & therapy, 13(3), R92. doi: 10.1186/ar3367
Vassar, R. (2001). The beta-secretase, BACE: a prime drug target for Alzheimer's disease. Journal of molecular neuroscience : MN, 17(2), 157-170. doi: 10.1385/jmn:17:2:157
Vassar, R. (2002). Beta-secretase (BACE) as a drug target for Alzheimer's disease. Advanced drug delivery reviews, 54(12), 1589-1602.
von Arnim, C. A., Kinoshita, A., Peltan, I. D., Tangredi, M. M., Herl, L., Lee, B. M., Spoelgen, R., Hshieh, T. T., Ranganathan, S., Battey, F. D., Liu, C. X., Bacskai, B. J., Sever, S., Irizarry, M. C., Strickland, D. K., & Hyman, B. T. (2005). The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate. The Journal of biological chemistry, 280(18), 17777-17785. doi: 10.1074/jbc.M414248200
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002). Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature, 416(6880), 535-539. doi: 10.1038/416535a
Wang, K. C., Tsai, C. P., Lee, C. L., Chen, S. Y., Lin, G. J., Yen, M. H., Sytwu, H. K., & Chen, S. J. (2013). alpha-Lipoic acid enhances endogenous peroxisome-proliferator-activated receptor-gamma to ameliorate experimental autoimmune encephalomyelitis in mice. Clinical science (London, England : 1979), 125(7), 329-340. doi: 10.1042/cs20120560
Wang, Y. P., Wu, Y., Li, L. Y., Zheng, J., Liu, R. G., Zhou, J. P., Yuan, S. Y., Shang, Y., & Yao, S. L. (2011). Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-kappaB and MAPKs in BV-2 microglial cells. Journal of neuroinflammation, 8, 95. doi: 10.1186/1742-2094-8-95
Waring, S. C., & Rosenberg, R. N. (2008). Genome-wide association studies in Alzheimer disease. Archives of neurology, 65(3), 329-334. doi: 10.1001/archneur.65.3.329
Weiner, H. L., & Frenkel, D. (2006). Immunology and immunotherapy of Alzheimer's disease. Nature reviews. Immunology, 6(5), 404-416. doi: 10.1038/nri1843
Weller, R. O., Djuanda, E., Yow, H. Y., & Carare, R. O. (2009). Lymphatic drainage of the brain and the pathophysiology of neurological disease. Acta neuropathologica, 117(1), 1-14. doi: 10.1007/s00401-008-0457-0
Wildsmith, K. R., Holley, M., Savage, J. C., Skerrett, R., & Landreth, G. E. (2013). Evidence for impaired amyloid beta clearance in Alzheimer's disease. Alzheimer's research & therapy, 5(4), 33. doi: 10.1186/alzrt187
Wisniewski, T., & Frangione, B. (1992). Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. Neuroscience letters, 135(2), 235-238.
Yamanaka, M., Ishikawa, T., Griep, A., Axt, D., Kummer, M. P., & Heneka, M. T. (2012). PPARgamma/RXRalpha-induced and CD36-mediated microglial amyloid-beta phagocytosis results in cognitive improvement in amyloid precursor protein/presenilin 1 mice. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32(48), 17321-17331. doi: 10.1523/jneurosci.1569-12.2012
Yan, P., Hu, X., Song, H., Yin, K., Bateman, R. J., Cirrito, J. R., Xiao, Q., Hsu, F. F., Turk, J. W., Xu, J., Hsu, C. Y., Holtzman, D. M., & Lee, J. M. (2006). Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. The Journal of biological chemistry, 281(34), 24566-24574. doi: 10.1074/jbc.M602440200
Yan, S. D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., Slattery, T., Zhao, L., Nagashima, M., Morser, J., Migheli, A., Nawroth, P., Stern, D., & Schmidt, A. M. (1996). RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature, 382(6593), 685-691. doi: 10.1038/382685a0
Yang, C. N., Shiao, Y. J., Shie, F. S., Guo, B. S., Chen, P. H., Cho, C. Y., Chen, Y. J., Huang, F. L., & Tsay, H. J. (2011). Mechanism mediating oligomeric Abeta clearance by naive primary microglia. Neurobiology of disease, 42(3), 221-230. doi: 10.1016/j.nbd.2011.01.005
Zhang, C. E., Wei, W., Liu, Y. H., Peng, J. H., Tian, Q., Liu, G. P., Zhang, Y., & Wang, J. Z. (2009). Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain. The American journal of pathology, 174(4), 1481-1491. doi: 10.2353/ajpath.2009.081036
Zhuo, J. M., & Pratico, D. (2010). Acceleration of brain amyloidosis in an Alzheimer's disease mouse model by a folate, vitamin B6 and B12-deficient diet. Experimental gerontology, 45(3), 195-201. doi: 10.1016/j.exger.2009.12.005