scholarly journals Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta

Neuron ◽  
2013 ◽  
Vol 78 (4) ◽  
pp. 631-643 ◽  
Author(s):  
Ana Griciuc ◽  
Alberto Serrano-Pozo ◽  
Antonio R. Parrado ◽  
Andrea N. Lesinski ◽  
Caroline N. Asselin ◽  
...  
2022 ◽  
pp. 1-15
Author(s):  
Kaitlyn E. Stepler ◽  
Taneisha R. Gillyard ◽  
Calla B. Reed ◽  
Tyra M. Avery ◽  
Jamaine S. Davis ◽  
...  

African American/Black adults are twice as likely to have Alzheimer’s disease (AD) compared to non-Hispanic White adults. Genetics partially contributes to this disparity in AD risk, among other factors, as there are several genetic variants associated with AD that are more prevalent in individuals of African or European ancestry. The phospholipid-transporting ATPase ABCA7 (ABCA7) gene has stronger associations with AD risk in individuals with African ancestry than in individuals with European ancestry. In fact, ABCA7 has been shown to have a stronger effect size than the apolipoprotein E (APOE) ɛ4 allele in African American/Black adults. ABCA7 is a transmembrane protein involved in lipid homeostasis and phagocytosis. ABCA7 dysfunction is associated with increased amyloid-beta production, reduced amyloid-beta clearance, impaired microglial response to inflammation, and endoplasmic reticulum stress. This review explores the impact of ABCA7 mutations that increase AD risk in African American/Black adults on ABCA7 structure and function and their contributions to AD pathogenesis. The combination of biochemical/biophysical and ‘omics-based studies of these variants needed to elucidate their downstream impact and molecular contributions to AD pathogenesis is highlighted.


2012 ◽  
Vol 15 (3) ◽  
pp. 286-295 ◽  
Author(s):  
Derrek P. Hibar ◽  
Neda Jahanshad ◽  
Jason L. Stein ◽  
Omid Kohannim ◽  
Arthur W. Toga ◽  
...  

The development of late-onset Alzheimer's disease (LOAD) is under strong genetic control and there is great interest in the genetic variants that confer increased risk. The Alzheimer's disease risk gene, growth factor receptor bound protein 2-associated protein (GAB2), has been shown to provide a 1.27–1.51 increased odds of developing LOAD for rs7101429 major allele carriers, in case-control analysis. GAB2 is expressed across the brain throughout life, and its role in LOAD pathology is well understood. Recent studies have begun to examine the effect of genetic variation in the GAB2 gene on differences in the brain. However, the effect of GAB2 on the young adult brain has yet to be considered. Here we found a significant association between the GAB2 gene and morphological brain differences in 755 young adult twins (469 females) (M = 23.1, SD = 3.1 years), using a gene-based test with principal components regression (PCReg). 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.


2006 ◽  
Vol 44 (1) ◽  
pp. e63-e63 ◽  
Author(s):  
L. Bertram ◽  
K. Mullin ◽  
M. Parkinson ◽  
M. Hsiao ◽  
T. J Moscarillo ◽  
...  

2018 ◽  
Vol 71 ◽  
pp. 266.e11-266.e24 ◽  
Author(s):  
Jenny Blechingberg ◽  
Annemarie Svane Aavild Poulsen ◽  
Mads Kjølby ◽  
Giulia Monti ◽  
Mariet Allen ◽  
...  

Cell Reports ◽  
2019 ◽  
Vol 28 (7) ◽  
pp. 1799-1813.e5 ◽  
Author(s):  
Shamsideen A. Ojelade ◽  
Tom V. Lee ◽  
Nikolaos Giagtzoglou ◽  
Lei Yu ◽  
Berrak Ugur ◽  
...  

2016 ◽  
Vol 12 ◽  
pp. P457-P458
Author(s):  
Anna L. Burt ◽  
Rhian S. Thomas ◽  
Melanie L. Dunstan ◽  
Rebecca Sims ◽  
Julie Williams

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