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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Copper stress induces zebrafish central neural system myelin defects via WNT/NOTCH-hoxb5b signaling and pou3f1/fam168a/fam168b DNA methylation.
Ting Zhang,Pengpeng Guan,WenYe Liu,Guang Zhao,Yaping Fang,Hui Fu,Jian-Fang Gui,Guoliang Li,Jing-Xia Liu +8 more
TL;DR: It is demonstrated that fam168b/pou3f1 and hoxb5b axis acted in a seesaw manner during fish embryogenesis: Cu induced the down-regulated expression of the WNT&NOTCH-hoxb 5b axis through the function of copper transporter cox17, coupled with the promoter methylation of genes fam168 b/ pou 3f1, making joint contributions to myelin defects in embryos.
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Relation of Retinal and Serum Lutein and Zeaxanthin to White Matter Integrity in Older Adults: A Diffusion Tensor Imaging Study.
Catherine M Mewborn,Douglas P. Terry,Lisa M. Renzi-Hammond,Billy R. Hammond,L. Stephen Miller +4 more
TL;DR: The current study is among the first to use neuroimaging to measure the relation of L&Z to brain structure in vivo and confirms previous findings that L &Z influence white matter integrity, particularly in regions vulnerable to age-related decline.
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Genetic risk of dementia modifies obesity effects on white matter myelin in cognitively healthy adults
Jilu P. Mole,Fabrizio Fasano,John Evans,Rebecca Sims,Derek A. Hamilton,Emma Jane Kidd,Claudia Metzler-Baddeley,Claudia Metzler-Baddeley +7 more
TL;DR: It is suggested that genetic risk modifies the impact of obesity on WM myelin consistent with neuroglia models of aging and late-onset Alzheimer's disease.
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Imaging and quantification of iron-oxide nanoparticles (IONP) using MP-RAGE and UTE based sequences.
Wen Hong,Wen Hong,Qun He,Shujuan Fan,Michael Carl,Hongda Shao,Jun Chen,Eric Y. Chang,Eric Y. Chang,Jiang Du +9 more
TL;DR: To investigate two‐dimensional and three‐dimensional ultrashort echo time (UTE) and 3D magnetization‐prepared rapid gradient‐echo sequences for the imaging of iron‐oxide nanoparticles (IONP).
Alzheimer's disease risk gene, GAB2, is associated with regional brain volume differences in 755 young healthy twins
Derrek P. Hibar,Neda Jahanshad,Jason L. Stein,Omid Kohannim,Arthur W. Toga,Sarah E. Medland,Narelle K. Hansell,Katie L. McMahon,G. I. de Zubicaray,Grant W. Montgomery,Nicholas G. Martin,Margaret J. Wright,Paul M. Thompson +12 more
TL;DR: Detectable differences in brain morphology are therefore associated with variation in the GAB2 gene, even in young adults, long before the typical age of onset of Alzheimer's disease.
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.