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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Essential roles of plexin-B3 + oligodendrocyte precursor cells in the pathogenesis of Alzheimer's disease
Naomi Nihonmatsu-Kikuchi,Xiu-Jun Yu,Xiu-Jun Yu,Yoshiki Matsuda,Nobuyuki Ozawa,Taeko Ito,Kazuhito Satou,Tadashi Kaname,Yasushi Iwasaki,Akio Akagi,Mari Yoshida,Shuta Toru,Katsuiku Hirokawa,Akihiko Takashima,Masato Hasegawa,Toshiki Uchihara,Yoshitaka Tatebayashi +16 more
TL;DR: In this paper, the role of oligodendrocyte lineage cells, the largest glial population in the adult central nervous system (CNS), in the pathogenesis of Alzheimer's disease (AD) remains elusive.
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Mitochondrial DNA variation in Alzheimer’s disease reveals a unique microprotein called SHMOOSE
Brendan Miller,Su-Jeong Kim,Hemal H. Mehta,Kevin Cao,Hiroshi Kumagai,Neehar Thumaty,Naphada Leelaprachakul,Henry Jiao,Joan Vaughan,Jolene K. Diedrich,Alan Saghatelian,Thalida Em Arpawong,Eileen M. Crimmins,Nilufer Ertekin-Taner,Meral A Tubi,Evan T Hare,Meredith N. Braskie,Léa Décarie-Spain,Scott E. Kanoski,Francine Grodstein,David A. Bennett,Lu Zhao,Arthur W. Toga,Junxiang Wan,Kelvin Yen,Pinchas Cohen +25 more
TL;DR: SHMOOSE acted on the brain following intracerebroventricular administration, differentiated mitochondrial gene expression in multiple models, localized to mitochondria, bound the inner mitochondrial membrane protein mitofilin, and boosted mitochondrial oxygen consumption, and has vast implications for the fields of neurobiology, Alzheimer's disease, and microproteins.
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Increased expression of myelin-associated genes in frontal cortex of SNCA overexpressing rats and Parkinson's disease patients.
Thomas Hentrich,Zinah Wassouf,Christine Ehrhardt,Eva Haas,James D. Mills,Eleonora Aronica,Tiago F. Outeiro,Jeannette Hübener-Schmid,Olaf Riess,Nicolas Casadei,Julia M. Schulze-Hentrich +10 more
TL;DR: The results highlight that even for a group of functionally linked genes distinct interference mechanisms may underlie disease progression that cannot be distinguished by examining the terminal point alone but instead require longitudinal interrogation of the system.
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A tough trek in the development of an anti-amyloid therapy for Alzheimer's disease: Do we see hope in the distance?
TL;DR: Aducanumab showed some subtle benefit in some mild Alzheimer's patients as discussed by the authors , however, the efficacy of the drug was limited and the conditions under which the drug should be administered were modified.
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Social Cognition and White Matter: Connectivity and Cooperation.
TL;DR: C cerebral white matter has expanded even more robustly than the neocortex, coinciding with the emergence of social cognition, and the contribution of white matter to social cognition can be conceptualized as the enhancement of cooperation through brain connectivity.
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.