Alzheimer's disease as homeostatic responses to age-related myelin breakdown
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TLDR
This work delineates empirically testable mechanisms of action for genes underlying FAD and LOAD and provides "upstream" treatment targets and reframes key observations such as axonal transport disruptions, formation of axonal swellings/sphenoids and neuritic plaques, and proteinaceous deposits as by-products of homeostatic myelin repair processes.Citations
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Hallmarks of Alzheimer’s Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain
Ira Espuny-Camacho,Amaia M. Arranz,Mark Fiers,An Snellinx,Kunie Ando,Sebastian Munck,Jérôme Bonnefont,Laurie Lambot,Nikky Corthout,Lorna Omodho,Elke Vanden Eynden,Enrico Radaelli,Ina Tesseur,Selina Wray,Andreas Ebneth,John Hardy,Karelle Leroy,Jean Pierre Brion,Pierre Vanderhaeghen,Pierre Vanderhaeghen,Bart De Strooper,Bart De Strooper +21 more
TL;DR: This novel chimeric model for AD displays human-specific pathological features and allows the analysis of different genetic backgrounds and mutations during the course of the disease.
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Breakdown of brain connectivity between normal aging and Alzheimer's disease: a structural k-core network analysis.
Madelaine Daianu,Neda Jahanshad,Talia M. Nir,Arthur W. Toga,Clifford R. Jack,Michael Weiner,Michael Weiner,Paul M. Thompson +7 more
TL;DR: Network disruptions were found, as connections were lost in AD, and a variety of measures sensitive to anatomical network topology, including the structural backbone--the so-called "k-core"--of the anatomical network, and the nodal degree were computed.
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Targeting Neuroinflammation to Treat Alzheimer’s Disease
A. Ardura-Fabregat,Erik Boddeke,Antonio Boza-Serrano,S. Brioschi,Sergio Castro-Gomez,K. Ceyzériat,K. Ceyzériat,Cira Dansokho,T. Dierkes,T. Dierkes,Géraldine Gelders,Michael T. Heneka,Michael T. Heneka,Lianne Hoeijmakers,A. Hoffmann,Leonardo Iaccarino,S. Jahnert,K. Kuhbandner,Gary E. Landreth,Niklas Lonnemann,Peter-Andreas Löschmann,Róisín M. McManus,Agnes Paulus,Kitty Reemst,J. M. Sanchez-Caro,A. Tiberi,A. Van der Perren,A. Vautheny,A. Vautheny,Carmen Venegas,A. Webers,Patrick Weydt,Teodora Stella Wijasa,Xianyuan Xiang,Yiyi Yang +34 more
TL;DR: The principal cellular and molecular players in inflammation as they pertain to AD are described, modifying factors are examined, and potential future therapeutic targets are discussed.
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Common Alzheimer's Disease Risk Variant Within the CLU Gene Affects White Matter Microstructure in Young Adults
Meredith N. Braskie,Neda Jahanshad,Jason L. Stein,Marina Barysheva,Katie L. McMahon,Greig I. de Zubicaray,Nicholas G. Martin,Margaret J. Wright,John M. Ringman,Arthur W. Toga,Paul M. Thompson +10 more
TL;DR: In this paper, a newly confirmed genetic risk allele C of the clusterin (CLU) gene variant rs11136000 is carried by ∼88% of Caucasians and the C allele confers a 1.16 greater odds of developing late-onset Alzheimer's disease than the T allele.
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Direct binding of cholesterol to the amyloid precursor protein: An important interaction in lipid-Alzheimer's disease relationships?
TL;DR: Binding of cholesterol to C99 appears to favor the amyloidogenic pathway in cells by promoting localization of C99 in lipid rafts, which may down-regulate ApoE-mediated cholesterol uptake and cholesterol biosynthesis.
References
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The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,Dennis J. Selkoe +1 more
TL;DR: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β-peptide in plaques in brain tissue and the rest of the disease process is proposed to result from an imbalance between Aβ production and Aβ clearance.
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Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
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Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.
Robert D. Terry,Eliezer Masliah,David P. Salmon,Nelson Butters,Richard DeTeresa,Robert Hill,Lawrence A. Hansen,Robert Katzman +7 more
TL;DR: Both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of patients with Alzheimer's disease and 9 neuropathologically normal subjects reveal very powerful correlations with all three psychological assays.
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Alzheimer's Disease Is a Synaptic Failure
TL;DR: Mounting evidence suggests that this syndrome begins with subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration, and that the synaptic dysfunction is caused by diffusible oligomeric assemblies of the amyloid β protein.
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Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory.
Ganesh M. Shankar,Shaomin Li,Tapan Mehta,Amaya Garcia-Munoz,Nina E. Shepardson,Imelda M. Smith,Francesca Brett,Michael A. Farrell,Michael J. Rowan,Cynthia A. Lemere,Ciaran M. Regan,Dominic M. Walsh,Bernardo L. Sabatini,Dennis J. Selkoe +13 more
TL;DR: It is concluded that soluble Aβ oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species.