Why therapies for Alzheimer's disease do not work: Do we have consensus over the path to follow?

Ageing Research Reviews

Volumn 25, Issue , 2016, Pages 70-84

  Amtul, Zareen ^a  

^a UNIVERSITY OF KARACHI   (Pakistan)

Author keywords

Amyloid; Animal models; Inflammation; Oxidative stress; Tau; Vascuar

Indexed keywords

AMYLOID BETA PROTEIN; OLIGOMER; TAU PROTEIN;

AGE; ALZHEIMER DISEASE; AMNESIA; COMPLEMENT SYSTEM; CONSENSUS; GENE MUTATION; HUMAN; IMMUNIZATION; MUTATION; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PROTEIN FUNCTION; PROTEIN METABOLISM; PROTEIN PROCESSING; REVIEW; TRANSGENIC MOUSE; TREATMENT FAILURE; ANIMAL; DISEASE MODEL;

ALZHEIMER DISEASE; ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; TREATMENT FAILURE;

EID: 84951573991     PISSN: 15681637     EISSN: 18729649     Source Type: Journal    
DOI: 10.1016/j.arr.2015.09.003     Document Type: Review

References (196)

1. Aizenstein H.J., Nebes R.D., Saxton J.A., et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch. Neurol. 2008, 65(November):1509-1517.
2. Alzheimer's disease international. World Alzheimer Report 2009.
3. Amtul Z., Rahman A.U. Neural plasticity and memory: molecular mechanism. Rev. Neurosci. 2015, 26. 253-268.
4. Amtul Z., Hepburn J.D. Protein markers of cerebrovascular disruption of neurovascular unit: immunohistochemical and imaging approaches. Rev. Neurosci. 2014, 25. 481-507.
5. Amtul Z., Rahman A.U. Neural plasticity and memory: is memory encoded in hydrogen bonding patterns?. Neuroscientist 2014, 28(AUGUST).
6. Amtul Z., Lewis P.A., Piper S., et al. A presenilin 1 mutation associated with familial frontotemporal dementia inhibits gamma-secretase cleavage of APP and notch. Neurobiol. Dis. 2002, 269-273.
7. Amtul Z., Park J.W., Murphy M.P., Siddiqui R.A., Choudhary M.I. Dietary lipids and Alzheimer's disease 9. Curr. Alzheimer Res. 2013, 542-548.
8. Arriagada P.V., Growdon J.H., Hedley-Whyte E.T., Hyman B.T. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 1992, 42(MARCH):631-639.
9. Ashe K.H. Mechanisms of memory loss in Abeta and tau mouse models. Biochem. Soc. Trans. 2005, 33(AUGUST):591-594.
10. Atwood C.S., Martins R.N., Smith M.A., Perry G. Senile plaque composition and posttranslational modification of amyloid-beta peptide and associated proteins. Peptides 2002, 23(July):1343-1350.
11. Atwood C.S., Obrenovich M.E., Liu T., et al. Amyloid-beta: a chameleon walking in two worlds: a review of the trophic and toxic properties of amyloid-beta. Brain Res. Brain Res. Rev. 2003, 1-16.
12. Austin L., Arendash G.W., Gordon M.N., et al. Short-term beta-amyloid vaccinations do not improve cognitive performance in cognitively impaired APP+PS1 mice. Behav. Neurosci. 2003, 478-484.
13. Bateman R.J., Munsell L.Y., Morris J.C., Swarm R., Yarasheski K.E., Holtzman D.M. Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat. Med. 2006, 12(July):856-861.
14. Bennett D.A., Schneider J.A., Wilson R.S., Bienias J.L., Arnold S.E. Neurofibrillary tangles mediate the association of amyloid load with clinical Alzheimer disease and level of cognitive function. Arch. Neurol. 2004, 61(MARCH):378-384.
15. Bian H., Van S., wieten J.C., Leight S., et al. CSF biomarkers in frontotemporal lobar degeneration with known pathology. Neurology 2008, 70(May (6)):1827-1835.
16. Bonda D.J., Wang X., Lee H.G., Smith M.A., Perry G., Zhu X. Neuronal failure in Alzheimer's disease: a view through the oxidative stress looking-glass. Neurosci. Bull. 2014, 243-252.
17. Borchelt D.R., Thinakaran G., Eckman C.B., et al. Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 1996, 17(November):1005-1013.
18. Borchelt D.R., Ratovitski T., van L.J., et al. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron 1997, 19(OCTOBER):939-945.
19. Braak H., Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol. Aging 1997, 351-357.
20. Braak H., Braak E., Bohl J., Reintjes R. Age, neurofibrillary changes, A beta-amyloid and the onset of Alzheimer's disease. Neurosci Lett. 1996, 210(May (31)):87-90.
21. Bradt B.M., Kolb W.P., Cooper N.R. Complement-dependent proinflammatory properties of the Alzheimer's disease beta-peptide. J. Exp. Med. 1998, 188(AUGUST(3)):431-438.
22. Breteler M.M. Vascular involvement in cognitive decline and dementia. Epidemiologic evidence from the Rotterdam Study and the Rotterdam Scan Study. Ann. N. Y. Acad. Sci. 2000, 903(APRIL):457-465.
23. Brosseron F., Krauthausen M., Kummer M., Heneka M.T. Body fluid cytokine levels in mild cognitive impairment and Alzheimer's disease: a comparative overview. Mol. Neurobiol. 2014, 534-544.
24. Brouillette J., Caillierez R., Zommer N., et al. Neurotoxicity and memory deficits induced by soluble low-molecular-weight amyloid-beta1-42 oligomers are revealed in vivo by using a novel animal model. J. Neurosci. 2012, 32(JUNE (6)):7852-7861.
25. Buee L., Hof P.R., Bouras C., et al. Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing disorders. Acta Neuropathol. 1994, 87:469-480.
26. Bugiani O., Giaccone G., Rossi G., et al. Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP. Arch. Neurol. 2010, 67(AUGUST):987-995.
27. Cairns N.J., Ikonomovic M.D., Benzinger T., et al. Absence of Pittsburgh compound B detection of cerebral amyloid beta in a patient with clinical, cognitive, and cerebrospinal fluid markers of Alzheimer disease: a case report. Arch. Neurol. 2009, 66(DECEMBER):1557-1562.
28. Calhoun M.E., Wiederhold K.H., Abramowski D., et al. Neuron loss in APP transgenic mice. Nature 1998, 395(OCTOBER (22)):755-756.
29. Carvalho C., Machado N., Mota P.C., et al. Type 2 diabetic and Alzheimer's disease mice present similar behavioral, cognitive, and vascular anomalies. J. Alzheimers Dis. 2013, 35:623-635.
30. Molecular Pathology of Alzheimer Disease 2013, Morgan & Claypool Life Sciences, San Rafael, California, pp 83. R.J. Castellani, G. Perry, Series (Eds.).
31. Castellani R.J., Smith M.A. Compounding artefacts with uncertainty, and an amyloid cascade hypothesis that is 'too big to fail'. J. Pathol. 2011, 147-152.
32. Caughlin S., Hepburn J.D., Park D.H., et al. Increased expression of simple ganglioside species GM2 and GM3 detected by MALDI imaging mass spectrometry in a combined rat model of abeta toxicity and stroke. PLoS One 2015, 10:e0130364.
33. Chakrabarty P., Tianbai L., Herring A., Ceballos-Diaz C., Das P., Golde T.E. Hippocampal expression of murine IL-4 results in exacerbation of amyloid deposition. Mol. Neurodegener. 2012, 7:36.
34. Chakrabarty P., Li A., Ceballos-Diaz C., et al. IL-10 alters immunoproteostasis in APP mice, increasing plaque burden and worsening cognitive behavior. Neuron 2015, 4(FEBRUARY(85)):519-533.
35. Chui D.H., Tanahashi H., Ozawa K., et al. Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Nat. Med. 1999, 560-564.
36. Citron M., Westaway D., Xia W., et al. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat. Med. 1997, 67-72.
37. Collie A., Maruff P. The neuropsychology of preclinical Alzheimer's disease and mild cognitive impairment. Neurosci. Biobehav. Rev. 2000, 365-374.
38. Coric V., van Dyck C.H., Salloway S., et al. Safety and tolerability of the gamma-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch. Neurol. 2012, 69(November):1430-1440.
39. Cruts M., Van B.C. Loss of progranulin function in frontotemporal lobar degeneration. Trends Genet. 2008, 186-194.
40. Cummings J.L. Cognitive and behavioral heterogeneity in Alzheimer's disease: seeking the neurobiological basis. Neurobiol. Aging 2000, 21(November):845-861.
41. Davis J.N., Chisholm J.C. The 'amyloid cascade hypothesis' of AD: decoy or real McCoy?. Trends Neurosci. 1997, 20(DECEMBER):558-559.
42. Davis D.G., Schmitt F.A., Wekstein D.R., Markesbery W.R. Alzheimer neuropathologic alterations in aged cognitively normal subjects. J. Neuropathol. Exp. Neurol. 1999, 58(APRIL):376-388.
43. Davis J., Xu F., Deane R., et al. Early-onset and robust cerebral microvascular accumulation of amyloid beta-protein in transgenic mice expressing low levels of a vasculotropic Dutch/Iowa mutant form of amyloid beta-protein precursor. J. Biol. Chem. 2004, 279(May (7)):20296-20306.
44. Devanand D.P., Pradhaban G., Liu X., et al. Hippocampal and entorhinal atrophyO in mild cognitive impairment: prediction of Alzheimer disease. Neurology 2007, 13(MARCH (68)):828-836.
45. Dodart J.C., May P. Overview on rodent models of Alzheimer's disease. Curr. Protoc. Neurosci. 2005, (Chapter 9): Unit.
46. Dodart J.C., Bales K.R., Gannon K.S., et al. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Nat. Neurosci. 2002, 5(May):452-457.
47. Duff K., Eckman C., Zehr C., et al. Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 1996, 383(OCTOBER (24)):710-713.
48. Dyrks T., Dyrks E., Masters C.L., Beyreuther K. Amyloidogenicity of rodent and human beta A4 sequences. FEBS Lett. 1993, 14(JUNE (324)):231-236.
49. Edison P., Archer H.A., Hinz R., et al. Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology 2007, 68(FEBRUARY(13)):501-508.
50. Fischer V.W., Siddiqi A., Yusufaly Y. Altered angioarchitecture in selected areas of brains with Alzheimer's disease. Acta Neuropathol. 1990, 79:672-679.
51. Fleischman D.A., Gabrieli J. Long-term memory in Alzheimer's disease. Curr. Opin. Neurobiol. 1999, 240-244.
52. Fotuhi M., Hachinski V., Whitehouse P.J. Changing perspectives regarding late-life dementia. Nat. Rev. Neurol. 2009, 5(DECEMBER):649-658.
53. Fox N.W. When, where, and how does Alzheimer's disease start?. Lancet Neurol. 2012, 11(DECEMBER):1017-1018.
54. Fraga M.F., Esteller M. Epigenetics and aging: the targets and the marks. Trends Genet. 2007, 413-418.
55. Games D., Adams D., Alessandrini R., et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 1995, 9(FEBRUARY(373)):523-527.
56. Gandy S. The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease. J. Clin. Invest. 2005, 115(May):1121-1129.
57. Ghosal K., Vogt D.L., Liang M., Shen Y., Lamb B.T., Pimplikar S.W. Alzheimer's disease-like pathological features in transgenic mice expressing the APP intracellular domain. Proc. Natl. Acad. Sci. U. S. A. 2009, 27(OCTOBER (27)):18367-18372.
58. Gilman S., Koller M., Black R.S., et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005, 64(May (10)):1553-1562.
59. Glenner G.G., Wong C.W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 1984, 120(May (16)):885-890.
60. Glenner G.G., Wong C.W. Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem. Biophys. Res. Commun. 1984, 122(AUGUST(16)):1131-1135.
61. Glynn P. A mechanism for organophosphate-induced delayed neuropathy. Toxicol. Lett. 2006, 15(MARCH (162)):94-97.
62. Goate A., Chartier-Harlin M.C., Mullan M., et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 1991, 349(FEBRUARY(21)):704-706.
63. Goldman W.P., Price J.L., Storandt M., et al. Absence of cognitive impairment or decline in preclinical Alzheimer's disease. Neurology 2001, 56(FEBRUARY(13)):361-367.
64. Gomez-Isla T., Price J.L., McKeel D.W., Morris J.C., Growdon J.H., Hyman B.T. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J. Neurosci. 1996, 15(July (16)):4491-4500.
65. Gomez-Isla T., Hollister R., West H., et al. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann. Neurol. 1997, 17-24.
66. Grabowski T.J., Cho H.S., Vonsattel J.P., Rebeck G.W., Greenberg S.M. Novel amyloid precursor protein mutation in an Iowa family with dementia and severe cerebral amyloid angiopathy. Ann. Neurol. 2001, 49(JUNE):697-705.
67. Greenberg S.M., Bacskai B.J., Hyman B.T. Alzheimer disease's double-edged vaccine. Nat. Med. 2003, 9(APRIL (390)):389.
68. Griffin W.S., Stanley L.C., Ling C., et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 1989, 86(OCTOBER):7611-7615.
69. Grossman M., Farmer J., Leight S., et al. Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease. Ann. Neurol. 2005, 721-729.
70. Haass C., Selkoe D.J. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat. Rev. Mol. Cell Biol. 2007, 101-112.
71. Hardy J., Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol. Sci. 1991, 12(OCTOBER):383-388.
72. Hardy J., Selkoe D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002, 297(July (19)):353-356.
73. Hardy J. The amyloid hypothesis for Alzheimer's disease: a critical reappraisal. J. Neurochem. 2009, 110(AUGUST):1129-1134.
74. Hatanpaa K., Brady D.R., Stoll J., Rapoport S.I., Chandrasekaran K. Neuronal activity and early neurofibrillary tangles in Alzheimer's disease. Ann. Neurol. 1996, 411-420.
75. Heilig E.A., Xia W., Shen J., Kelleher R.J., III A presenilin-1 mutation identified in familial Alzheimer disease with cotton wool plaques causes a nearly complete loss of gamma-secretase activity. J. Biol. Chem. 2010, 16(July (285)):22350-22359.
76. Hendriks L., van Duijn C.M., Cras P., et al. Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene. Nat. Genet. 1992, 1(JUNE):218-221.
77. Hensley K., Carney J.M., Mattson M.P., et al. A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 1994, 12(APRIL (91)):3270-3274.
78. Hensley K., Hall N., Subramaniam R., et al. Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation. J. Neurochem. 1995, 65(November):2146-2156.
79. Herrup K. Reimagining Alzheimer's disease-an age-based hypothesis. J. Neurosci. 2010, 30(DECEMBER (15)):16755-16762.
80. Hesse C., Rosengren L., Andreasen N., et al. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke. Neurosci. Lett. 2001, 19(JANUARY (297)):187-190.
81. Holcomb L., Gordon M.N., McGowan E., et al. Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat. Med. 1998, 4(JANUARY):97-100.
82. Holmes C., Boche D., Wilkinson D., et al. Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 2008, 372(July (19)):216-223.
83. Hong X., Bu L., Wang Y., et al. Increases in the risk of cognitive impairment and alterations of cerebral beta-amyloid metabolism in mouse model of heart failure. PLoS One 2013, 8:e63829.
84. Hsia A.Y., Masliah E., McConlogue L., et al. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc. Natl. Acad. Sci. U. S. A. 1999, 16(MARCH (96)):3228-3233.
85. Hsiao K., Chapman P., Nilsen S., et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 1996, 4(OCTOBER (274)):99-102.
86. Hutton M., Lendon C.L., Rizzu P., et al. Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 1998, 393(JUNE (18)):702-705.
87. Irizarry M.C., McNamara M., Fedorchak K., Hsiao K., Hyman B.T. APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1. J. Neuropathol. Exp. Neurol. 1997, 56(SEPTEMBER):965-973.
88. Jaikaran E.T., Clark A. Islet amyloid and type 2 diabetes: from molecular misfolding to islet pathophysiology. Biochim. Biophys. Acta. 2001, 1537(NOVEMBER(29)):179-203.
89. Jaturapatporn D., Isaac M.G., McCleery J., Tabet N. Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease. Cochrane Database Syst. Rev. 2012, 2:CD006378.
90. Ji Y., Urakami K., Adachi Y., Maeda M., Isoe K., Nakashima K.A., polipoprotein E. polymorphism in patients with Alzheimer's disease, vascular dementia and ischemic cerebrovascular disease. Dement. Geriatr. Cogn. Disord 1998, 9(SEPTEMBER):243-245.
91. Johnson K.A., Albert M.S. Perfusion abnormalities in prodromal AD. Neurobiol. Aging 2000, 21(MARCH):289-292.
92. Johnson K.A., Jones K., Holman B.L., et al. Preclinical prediction of Alzheimer's disease using SPECT. Neurology 1998, 50(JUNE):1563-1571.
93. Jonsson T., Atwal J.K., Steinberg S., et al. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 2012, 488(AUGUST(2)):96-99.
94. Kalaria R.N. The role of cerebral ischemia in Alzheimer's disease. Neurobiol Aging 2000, 21(MARCH):321-330.
95. Kane M.D., Lipinski W.J., Callahan M.J., et al. Evidence for seeding of beta -amyloid by intracerebral infusion of Alzheimer brain extracts in beta -amyloid precursor protein-transgenic mice. J. Neurosci. 2000, 20(May (15)):3606-3611.
96. Kang J.E., Lim M.M., Bateman R.J., et al. Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 2009, 326(NOVEMBER(12)):1005-1007.
97. Karran E., Mercken M., De S.B. The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat. Rev. Drug Discov. 2011, 10(SEPTEMBER):698-712.
98. Knopman D.S., Parisi J.E., Salviati A., et al. Neuropathology of cognitively normal elderly. J. Neuropathol. Exp. Neurol. 2003, 62(November):1087-1095.
99. Kogure D., Matsuda H., Ohnishi T., et al. Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT. J. Nucl. Med. 2000, 41(July):1155-1162.
100. Koistinaho M., Ort M., Cimadevilla J.M., et al. Specific spatial learning deficits become severe with age in beta -amyloid precursor protein transgenic mice that harbor diffuse beta -amyloid deposits but do not form plaques. Proc. Natl. Acad. Sci. U. S. A. 2001, 4(DECEMBER (98)):14675-14680.
101. Koudinov A.R., Berezov T.T. Alzheimer's amyloid-beta (A beta) is an essential synaptic protein, not neurotoxic junk. Acta Neurobiol. Exp. (Wars) 2004, 64:71-79.
102. Kowalik-Jankowska T., Ruta-Dolejsz M., Wisniewska K., Lankiewicz L., Kozlowski H. Possible involvement of copper(II) in Alzheimer disease. Environ. Health Perspect. 2002, 110(OCTOBER Suppl. 5):869-870.
103. Krafft G.A., Klein W.L. ADDLs and the signaling web that leads to Alzheimer's disease. Neuropharmacology 2010, 59(SEPTEMBER):230-242.
104. Kuchibhotla K.V., Wegmann S., Kopeikina K.J., et al. Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo. Proc. Natl. Acad. Sci. U. S. A. 2014, 111(JANUARY (7)):510-514.
105. Kudinova N.V., Kudinov A.R., Berezov T.T. Amyloid beta: functional protein or biological junk?. Biomed Khim 2007, 53(MARCH):119-127.
106. Kuo Y.M., Kokjohn T.A., Beach T.G., et al. Comparative analysis of amyloid-beta chemical structure and amyloid plaque morphology of transgenic mouse and Alzheimer's disease brains. J. Biol. Chem. 2001, 20(APRIL (276)):12991-12998.
107. LaFerla F.M., Green K.N. Animal models of Alzheimer disease. Cold Spring Harbor Perspec.t Med. 2012, 2-November.
108. Laurent B., Thomas-Anterion C., Allegri R.F. Memory and dementia. Rev. Neurol. (Paris) 1998, 154(Suppl. 2):S33-S49.
109. Lee S., Fernandez E.J., Good T.A. Role of aggregation conditions in structure, stability, and toxicity of intermediates in the Abeta fibril formation pathway. Protein Sci. 2007, 16(APRIL):723-732.
110. Lewis J., McGowan E., Rockwood J., et al. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat. Genet. 2000, 25(AUGUST):402-405.
111. Lewis J., Dickson D.W., Lin W.L., et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 2001, 24(AUGUST(293)):1487-1491.
112. Li Y., Rinne J.O., Mosconi L., et al. Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer's disease. Eur. J. Nucl. Med. Mol. Imaging 2008, 35(DECEMBER):2169-2181.
113. Liberski P.P., Sikorska B., Hauw J.J., et al. Ultrastructural characteristics (or evaluation) of Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies or prion diseases. Ultrastruct. Pathol. 2010, 34(DECEMBER):351-361.
114. MacDonald M.E., Gines S., Gusella J.F., Wheeler V.C. Huntington's disease. Neuromolecular Med. 2003, 4:7-20.
115. Mastroeni D., McKee A., Grover A., Rogers J., Coleman P.D. Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer's disease. PLoS One 2009, 4:e6617.
116. McGeer P.L., McGeer E.G. The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol. 2013, 126(OCTOBER):479-497.
117. McGeer P.L., Schulzer M., McGeer E.G. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology 1996, 47(AUGUST):425-432.
118. Mecocci P., MacGarvey U., Beal M.F. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann. Neurol. 1994, 747-751.
119. Meyer J.S., Rauch G., Rauch R.A., Haque A. Risk factors for cerebral hypoperfusion, mild cognitive impairment, and dementia. Neurobiol. Aging 2000, 161-169.
120. Meyer-Luehmann M., Coomaraswamy J., Bolmont T., et al. Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host. Science 2006, 313(SEPTEMBER (22)):1781-1784.
121. Mintun M.A., Larossa G.N., Sheline Y.I., et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 2006, 67(AUGUST(8)):446-452.
122. Monro O.R., Mackic J.B., Yamada S., et al. Substitution at codon 22 reduces clearance of Alzheimer's amyloid-beta peptide from the cerebrospinal fluid and prevents its transport from the central nervous system into blood. Neurobiol. Aging 2002, 23(May):405-412.
123. Moreth J., Kroker K.S., Schwanzar D., et al. Globular and protofibrillar abeta aggregates impair neurotransmission by different mechanisms. Biochemistry 2013, 52(FEBRUARY(26)):1466-1476.
124. Morsch R., Simon W., Coleman P.D. Neurons may live for decades with neurofibrillary tangles. J. Neuropathol. Exp. Neurol. 1999, 58(February):188-197.
125. Mullane K., Williams M. Alzheimer's therapeutics: continued clinical failures question the validity of the amyloid hypothesis-but what lies beyond?. Biochem. Pharmacol. 2013, 85(FEBRUARY(1)):289-305.
126. Nalbantoglu J., Tirado-Santiago G., Lahsaini A., et al. Impaired learning and LTP in mice expressing the carboxy terminus of the Alzheimer amyloid precursor protein. Nature 1997, 29(May (387)):500-505.
127. Nell H.J., Whitehead S.N., Cechetto D.F. Age-dependent effect of beta-amyloid toxicity on basal forebrain cholinergic neurons and inflammation in the rat brain. Brain Pathol. 2014, 3.
128. Nicoll J.A., Wilkinson D., Holmes C., Steart P., Markham H., Weller R.O. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat. Med. 2003, 448-452.
129. Nikolaev A., McLaughlin T., O'Leary D.D., Tessier-Lavigne M. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 2009, 19(FEBRUARY(457)):981-989.
130. Nilsberth C., Westlind-Danielsson A., Eckman C.B., et al. The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nat. Neurosci. 2001, 4(SEPTEMBER):887-893.
131. Niwa K., Carlson G.A., Iadecola C. Exogenous A beta1-40 reproduces cerebrovascular alterations resulting from amyloid precursor protein overexpression in mice. J. Cereb. Blood Flow Metab. 2000, 20(DECEMBER):1659-1668.
132. Nunomura A., Perry G., Aliev G., et al. Oxidative damage is the earliest event in Alzheimer disease. J. Neuropathol. Exp. Neurol. 2001, 759-767.
133. Oddo S., Vasilevko V., Caccamo A., Kitazawa M., Cribbs D.H., LaFerla F.M. Reduction of soluble Abeta and tau, but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. J. Biol. Chem. 2006, 281(DECEMBER (22)):39413-39423.
134. Okamura N., Shinkawa M., Arai H., et al. [Prediction of progression in patients with mild cognitive impairment using IMP-SPECT]. Nihon Ronen Igakkai Zasshi 2000, 974-978.
135. Oksman M., Iivonen H., Hogyes E., et al. Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice 20. Neurobiol. Dis. 2006, 563-572.
136. Oyama F., Sawamura N., Kobayashi K., et al. Mutant presenilin 2 transgenic mouse: effect on an age-dependent increase of amyloid beta-protein 42 in the brain. J. Neurochem. 1998, 313-322.
137. Palmer A.M., Burns M.A. Selective increase in lipid peroxidation in the inferior temporal cortex in Alzheimer's disease. Brain Res. 1994, 645(May (9)):338-342.
138. Palmer J.C., Barker R., Kehoe P.G., Love S. Endothelin-1 is elevated in Alzheimer's disease and upregulated by amyloid-beta. J. Alzheimers Dis. 2012, 29:853-861.
139. Pennartz C.M., Ito R., Verschure P.F., Battaglia F.P., Robbins T.W. The hippocampal-striatal axis in learning, prediction and goal-directed behavior. Trends Neurosci. 2011, 548-559.
140. Perry V.H., Nicoll J.A., Holmes C. Microglia in neurodegenerative disease. Nat. Rev. Neurol. 2010, 6(APRIL):193-201.
141. Petrou M., Bohnen N.I., Muller M.L., Koeppe R.A., Albin R.L., Frey K.A. Abeta-amyloid deposition in patients with Parkinson disease at risk for development of dementia. Neurology 2012, 79(SEPTEMBER (11)):1161-1167.
142. Pimplikar S.W., Nixon R.A., Robakis N.K., Shen J., Tsai L.H. Amyloid-independent mechanisms in Alzheimer's disease pathogenesis. J. Neurosci. 2010, 30(NOVEMBER(10)):14946-14954.
143. Pimplikar S.W. Reassessing the amyloid cascade hypothesis of Alzheimer's disease. Int. J. Biochem. Cell Biol. 2009, 41(JUNE):1261-1268.
144. Plant L.D., Boyle J.P., Smith I.F., Peers C., Pearson H.A. The production of amyloid beta peptide is a critical requirement for the viability of central neurons. J. Neurosci. 2003, 23(July (2)):5531-5535.
145. Pohjasvaara T., Erkinjuntti T., Ylikoski R., Hietanen M., Vataja R., Kaste M. Clinical determinants of poststroke dementia. Stroke 1998, 29(JANUARY):75-81.
146. Prasansuklab A., Tencomnao T. Amyloidosis in Alzheimer's disease: the toxicity of amyloid beta (A beta), mechanisms of its accumulation and implications of medicinal plants for therapy. Evid Based Complement Altern. Med. 2013, 2013. 413808.
147. Pratico D. Oxidative stress hypothesis in Alzheimer's disease: a reappraisal. Trends Pharmacol. Sci. 2008, 29(DECEMBER):609-615.
148. Price J.L., Morris J.C. Tangles and plaques in nondemented aging and preclinical Alzheimer's disease. Ann. Neurol. 1999, 358-368.
149. ROTHM The natural history of mental disorder in old age. J. Ment. Sci. 1955, 101(APRIL):281-301.
150. Rapoport M., Dawson H.N., Binder L.I., Vitek M.P., Ferreira A. Tau is essential to beta -amyloid-induced neurotoxicity. Proc. Natl. Acad. Sci. U. S. A. 2002, 30(APRIL (99)):6364-6369.
151. Rebeck G.W., Perls T.T., West H.L., Sodhi P., Lipsitz L.A., Hyman B.T. Reduced apolipoprotein epsilon 4 allele frequency in the oldest old Alzheimer's patients and cognitively normal individuals. Neurology 1994, 44(AUGUST):1513-1516.
152. Reed M.N., Liu P., Kotilinek L.A., Ashe K.H. Effect size of reference memory deficits in the Morris water maze in Tg2576 mice. Behav Brain Res. 2010, 1(SEPTEMBER (212)):115-120.
153. Robakis N.K. Mechanisms of AD neurodegeneration may be independent of Abeta and its derivatives. Neurobiol. Aging 2011, 32(MARCH):372-379.
154. Roberson E.D., Scearce-Levie K., Palop J.J., et al. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 2007, 4(May (316)):750-754.
155. Robinson S.R., Bishop G.M. The search for an amyloid solution. Science 2002, 298(NOVEMBER(1)):962-964.
156. Robinson S.R., Bishop G.M. Abeta as a bioflocculant: implications for the amyloid hypothesis of Alzheimer's disease. Neurobiol. Aging 2002, 23(November):1051-1072.
157. Rodriguez G., Vitali P., Calvini P., et al. Hippocampal perfusion in mild Alzheimer's disease. Psychiatry Res. 2000, 100(DECEMBER (4)):65-74.
158. Rogers J., Cooper N.R., Webster S., et al. Complement activation by beta-amyloid in Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 1992, 1(NOVEMBER(89)):10016-10020.
159. Ruiz-Opazo N., Kosik K.S., Lopez L.V., Bagamasbad P., Ponce L.R., Herrera V.L. Attenuated hippocampus-dependent learning and memory decline in transgenic TgAPPswe Fischer-344 rats. Mol. Med. 2004, 10(JANUARY):36-44.
160. Savva G.M., Wharton S.B., Ince P.G., Forster G., Matthews F.E., Brayne C. Age, neuropathology, and dementia. N. Engl. J. Med. 2009, 28(May (360)):2302-2309.
161. Schenk D., Barbour R., Dunn W., et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999, 400(July (8)):173-177.
162. Schmidt M.L., Lee V.M., Saido T., et al. Amyloid plaques in Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex contain species of A beta similar to those found in the amyloid plaques of Alzheimer's disease and pathological aging. Acta Neuropathol. 1998, 95(February):117-122.
163. Schneider J.A., Arvanitakis Z., Bang W., Bennett D.A. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 2007, 11(DECEMBER (69)):2197-2204.
164. Schwab C., Hosokawa M., McGeer P.L. Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease. Exp. Neurol. 2004, 52-64.
165. Selkoe D.J. Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein. Ann. N. Y. Acad. Sci. 2000, 924:17-25.
166. Selkoe D.J. Resolving controversies on the path to Alzheimer's therapeutics. Nat. Med. 2011, 17(SEPTEMBER):1060-1065.
167. Shankar G.M., Bloodgood B.L., Townsend M., Walsh D.M., Selkoe D.J., Sabatini B.L. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J. Neurosci. 2007, 27(MARCH (14)):2866-2875.
168. Shaw L.M., Vanderstichele H., Knapik-Czajka M., et al. Cerebrospinal fluid biomarker sig in Alzheimer's disease neuroimaging initiative subjects. Ann. Neurol. 2009, 65(APRIL):403-413.
169. Smith M.A., Perry G., Richey P.L., et al. Oxidative damage in Alzheimer's. Nature 1996, 11(July (382)):120-121.
170. Smith M.A., Casadesus G., Joseph J.A., Perry G. Amyloid-beta and tau serve antioxidant functions in the aging and Alzheimer brain. Free Radic. Biol. Med. 2002, 1(NOVEMBER(33)):1194-1199.
171. Snitz B.E., Weissfeld L.A., Lopez O.L., et al. Cognitive trajectories associated with beta-amyloid deposition in the oldest-old without dementia. Neurology 2013, 80(APRIL (9)):1378-1384.
172. Snowdon D.A., Greiner L.H., Mortimer J.A., Riley K.P., Greiner P.A., Markesbery W.R. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 1997, 277(MARCH (12)):813-817.
173. Spillantini M.G., Murrell J.R., Goedert M., Farlow M.R., Klug A., Ghetti B. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc. Natl. Acad. Sci. U. S. A. 1998, 23(JUNE (95)):7737-7741.
174. Spires-Jones T.L., Stoothoff W.H., de C.A., Jones P.B., Hyman B.T. Tau pathophysiology in neurodegeneration: a tangled issue. Trends Neurosci. 2009, 32(MARCH):150-159.
175. Suter O.C., Sunthorn T., Kraftsik R., et al. Cerebral hypoperfusion generates cortical watershed microinfarcts in Alzheimer disease. Stroke 2002, 33(AUGUST):1986-1992.
176. Tanzi R.E. The genetics of Alzheimer disease. Cold Spring Harbor Perspect. Med. 2012, 2.
177. Thal D.R., Rub U., Orantes M., Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 2002, 58(JUNE (25)):1791-1800.
178. Thomas T., Thomas G., McLendon C., Sutton T., Mullan M. beta-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature 1996, 380(MARCH (2014)):168-171.
179. Tu S., Okamoto S., Lipton S.A., Xu H. Oligomeric Abeta-induced synaptic dysfunction in Alzheimer's disease. Mol. Neurodegener. 2014, 9:48.
180. Uylings H.B., de Brabander J.M. Neuronal changes in normal human aging and Alzheimer's disease. Brain Cogn. 2002, 49(AUGUST):268-276.
181. Van B.C., Haan J., Bakker E., et al. Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch). Science 1990, 248(JUNE (1)):1120-1122.
182. Villemagne V.L., Ataka S., Mizuno T., et al. High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types. Arch. Neurol. 2009, 66(DECEMBER (66)):1537-1544.
183. Vukic V., Callaghan D., Walker D., et al. Expression of inflammatory genes induced by beta-amyloid peptides in human brain endothelial s and in Alzheimer's brain is mediated by the JNK-AP1 signaling pathway. Neurobiol. Dis. 2009, 34(APRIL):95-106.
184. Wang X., Michaelis E.K. Selective neuronal vulnerability to oxidative stress in the brain. Front. Aging Neurosci. 2010, 2:12.
185. Wang R., Wang B., He W., Zheng H. Wild-type presenilin 1 protects against Alzheimer disease mutation-induced amyloid pathology. J. Biol. Chem. 2006, 2(JUNE (281)):15330-15336.
186. Watt A.D., Perez K.A., Rembach A., et al. Oligomers, fact or artefact? SDS-PAGE induces dimerization of beta-amyloid in human brain samples. Acta Neuropathol. 2013, 125(APRIL):549-564.
187. Westerman M.A., Cooper-Blacketer D., Mariash A., et al. The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. J. Neurosci. 2002, 22(MARCH (1)):1858-1867.
188. Wilson V.L., Jones P.A. DNA methylation decreases in aging but not in immortal cells. Science 1983, 3(JUNE (220)):1055-1057.
189. Wisniewski T., Ghiso J., Frangione B. Alzheimer's disease and soluble A beta. Neurobiol. Aging 1994, 15(MARCH):143-152.
190. Xekardaki A., Rodriguez C., Montandon M.L., Toma S., Tombeur E., Herrmann F.R., Zekry D., Lovblad K.O., Barkhof F., Giannakopoulos P., Haller S. Arterial spin labeling may contribute to the prediction of cognitive deterioration in healthy elderly individuals. Radiology 2015, 274(FEBRUARY(2)):490-499. 10.1148/radiol.14140680.
191. Yamanaka M., Ishikawa T., Griep A., Axt D., Kummer M.P., Heneka M.T. PPARgamma/RXRalpha-induced and CD36-mediated microglial amyloid-beta phagocytosis results in cognitive improvement in amyloid precursor protein/presenilin 1 mice. J. Neurosci. 2012, 32(NOVEMBER(28)):17321-17331.
192. Zahs K.R., Ashe K.H. 'Too much good news' - are Alzheimer mouse models trying to tell us how to prevent, not cure, Alzheimer's disease?. Trends Neurosci. 2010, 33(AUGUST):381-389.
193. Zhu C.W., Scarmeas N., Torgan R., et al. Clinical features associated with costs in early AD: baseline data from the predictors study. Neurology 2006, 66(APRIL (11)):1021-1028.
194. Zigman W.B., Devenny D.A., Krinsky-McHale S.J., et al. Alzheimer's disease in adults with down syndrome. Int. Rev. Res. Ment. Retard. 2008, 36(JANUARY (1)):103-145.
195. de la Torre J.C., Mussivand T. Can disturbed brain microcirculation cause Alzheimer's disease?. Neurol. Res. 1993, 146-153.
196. de la Torre J.C. Cardiovascular risk factors promote brain hypoperfusion leading to cognitive decline and dementia. Cardiovasc. Psychiatry Neurol. 2012, 2012:367516.