Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Multi-omics identification of haptoglobin as a novel target for increased Alzheimer's disease risk associated with obesity through inhibiting the phagocytosis of Aβ by disease-associated microglia.
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.
Qian Xiaohang, Wang Zhongxuan, Cui Peijing, Chen Siyue, Xue Yang, Yang Yawen, Xu Jianhua, Liu Xiaoli, Ding Gangyu, Tang Huidong
Аннотация
INTRODUCTION: Obesity may increase Alzheimer's disease (AD) risk, yet the underlying mechanisms remain unclear.
METHODS: We investigated this link through global epidemiology, Mendelian randomization (MR), transcriptomics, clinical cohort validation, and mechanistic exploration.
RESULTS: High body mass index (BMI)-attributable AD disability-adjusted life years and deaths increased 4-fold from 1990-2021, with projections indicating a tripling by 2050. MR analyses found that elevated BMI was genetically related to increased AD risk. Haptoglobin (HP) was identified as a core mediator between them. HP expression was correlated with plasma AD biomarkers and cognitive scores. Mechanistically, HP localized to plaque-associated microglia and suppressed microglial amyloid beta (Aβ) phagocytosis and DNAX activating protein of 12 kDa (Dap12)/Spleen tyrosine kinase (Syk) pathway with modulating disease-associated microglial transcriptional programs.
CONCLUSION: This study identified HP as a strong candidate mediator linking obesity to AD pathogenesis through inhibiting the phagocytosis of Aβ by microglia.
METHODS: We investigated this link through global epidemiology, Mendelian randomization (MR), transcriptomics, clinical cohort validation, and mechanistic exploration.
RESULTS: High body mass index (BMI)-attributable AD disability-adjusted life years and deaths increased 4-fold from 1990-2021, with projections indicating a tripling by 2050. MR analyses found that elevated BMI was genetically related to increased AD risk. Haptoglobin (HP) was identified as a core mediator between them. HP expression was correlated with plasma AD biomarkers and cognitive scores. Mechanistically, HP localized to plaque-associated microglia and suppressed microglial amyloid beta (Aβ) phagocytosis and DNAX activating protein of 12 kDa (Dap12)/Spleen tyrosine kinase (Syk) pathway with modulating disease-associated microglial transcriptional programs.
CONCLUSION: This study identified HP as a strong candidate mediator linking obesity to AD pathogenesis through inhibiting the phagocytosis of Aβ by microglia.