Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
APOE*4 risk-modifying genes and drug targets in Alzheimer's disease through cell-type-specific genomic analyses.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zeng Youjie, Cook Noah, Yang Chenyu, Sivasankaran Sathesh K, Fujita Masashi, Gardell Zachary A, Le Guen Yann, Shigemizu Daichi, Ozaki Kouichi, Morizono Takashi, Hara Norikazu, Miyashita Akinori, Ikeuchi Takeshi, Pottier Cyril, Cruchaga Carlos, Napolioni Valerio, Corces M Ryan, Menon Vilas, Greicius Michael D, Belloy Michael E
Аннотация
INTRODUCTION: Genetics studies can identify drug targets that counteract the effects of the apolipoprotein E ε4 allele (APOE*4) on Alzheimer's disease (AD) but have remained limited in power and crucially did not assess genetic findings with regard to APOE*4's cell-type-specific impact on pathobiology.
METHODS: We conducted a novel APOE*4-stratified genome-wide association study (GWAS) of AD (N = 447,669) and integrated results with brain cell-type-specific multi-omics data to identify APOE*4 and cell-type-specific AD genes, followed by compound and drug repurposing.
RESULTS: In APOE*4 non-carriers (APOE*4-) and carriers (APOE*4+), we respectively identified 33 and 11 cell type-gene pairs with strong prioritization support. Oligodendrocytes displayed the largest proportion of APOE*4+ genes. Several genes were druggable and pinpointed APOE*4-stratified drugs or compounds.
DISCUSSION: We identified a set of APOE*4-stratified genes that may be causal for AD through brain cell-type-specific mechanisms. We additionally identified compounds that may shed light on therapeutic avenues for treating AD based on an individual's APOE*4 status.
METHODS: We conducted a novel APOE*4-stratified genome-wide association study (GWAS) of AD (N = 447,669) and integrated results with brain cell-type-specific multi-omics data to identify APOE*4 and cell-type-specific AD genes, followed by compound and drug repurposing.
RESULTS: In APOE*4 non-carriers (APOE*4-) and carriers (APOE*4+), we respectively identified 33 and 11 cell type-gene pairs with strong prioritization support. Oligodendrocytes displayed the largest proportion of APOE*4+ genes. Several genes were druggable and pinpointed APOE*4-stratified drugs or compounds.
DISCUSSION: We identified a set of APOE*4-stratified genes that may be causal for AD through brain cell-type-specific mechanisms. We additionally identified compounds that may shed light on therapeutic avenues for treating AD based on an individual's APOE*4 status.