Journal ArticleDOI
Apolipoprotein E: Cholesterol metabolism and Alzheimer's pathology
Reads0
Chats0
TLDR
In this review, some important historic and scientific aspects of the progress in understanding the role of the cholesterol transporter ApoE in the brain are summarized, and how the isoformApoE4 contributes to AD pathology is summarized.Abstract:
Abstract Age is the greatest risk factor for Alzheimer’s disease (AD). Today, due to an increase in global life expectancy, AD-related deaths are ranked as the sixth most common cause of death. The allele isoform ɛ4 of apolipoprotein E (ApoE4) is the most important genetic risk factor for AD. Three ApoE isoforms are common in humans: ApoE2, ApoE3, and ApoE4. ApoE3 is the most frequent isoform and considered neutral with regards to AD, whereas the isoform ApoE2 is protective. Thus it is important to understand how ApoE isoforms affect amyloid-β (Aβ) and tau toxicity, the key drivers of AD pathology. Aβ and tau accumulate to form the hallmarks of AD, plaques and neurofibrillary tangles, respectively. ApoE, primarily expressed by astrocytes, is the major lipid transporter in the brain. In this review I summarize some important historic and scientific aspects of our progress in understanding the role of the cholesterol transporter ApoE in the brain, and how the isoform ApoE4 contributes to AD pathology.read more
References
More filters
Journal ArticleDOI
Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis
Lindsay A. Farrer,L. Adrienne Cupples,Jonathan L. Haines,Bradley T. Hyman,Walter A. Kukull,Richard Mayeux,Richard H. Myers,Margaret A. Pericak-Vance,Neil Risch,Cornelia M. van Duijn +9 more
TL;DR: The APOE∈4 allele represents a major risk factor for AD in all ethnic groups studied, across all ages between 40 and 90 years, and in both men and women.
Journal ArticleDOI
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Hadas Keren-Shaul,Amit Spinrad,Assaf Weiner,Assaf Weiner,Orit Matcovitch-Natan,Raz Dvir-Szternfeld,Tyler K. Ulland,Eyal David,Kuti Baruch,David Lara-Astaiso,Beáta Tóth,Shalev Itzkovitz,Marco Colonna,Michal Schwartz,Ido Amit +14 more
TL;DR: A novel microglia type associated with neurodegenerative diseases (DAM) is described and it is revealed that the DAM program is activated in a two-step process that involves downregulation of microglian checkpoints, followed by activation of a Trem2-dependent program.
Journal ArticleDOI
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
TL;DR: The severity of dementia was positively related to the number of NFTs in neocortex, but not to the degree of SP deposition, and N FTs accumulate in a consistent pattern reflecting hierarchic vulnerability of individual cytoarchitectural fields.
Journal ArticleDOI
Brain Infarction and the Clinical Expression of Alzheimer Disease: The Nun Study
David A. Snowdon,Lydia H. Greiner,James A. Mortimer,Kathryn P. Riley,Philip A. Greiner,William R. Markesbery +5 more
TL;DR: Findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
Journal ArticleDOI
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases
Susanne Krasemann,Susanne Krasemann,Charlotte Madore,Ron Cialic,Caroline Baufeld,Narghes Calcagno,Rachid El Fatimy,Lien Beckers,Elaine O’Loughlin,Yang Xu,Zain Fanek,David J. Greco,Scott T. Smith,George Tweet,Zachary Humulock,Tobias Zrzavy,Patricia Conde-Sanroman,Mar Gacias,Zhiping Weng,Hao Chen,Emily C. Tjon,Fargol Mazaheri,Kristin Hartmann,Asaf Madi,Jason D. Ulrich,Markus Glatzel,Anna Worthmann,Joerg Heeren,Bogdan Budnik,Cynthia A. Lemere,Tsuneya Ikezu,Frank L. Heppner,Vladimir Litvak,David M. Holtzman,Hans Lassmann,Howard L. Weiner,Jordi Ochando,Christian Haass,Oleg Butovsky +38 more
TL;DR: The TREM2-APOE pathway is identified as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target that could aid in the restoration of homeostatic microglia.