Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Alzheimer's disease risk single nucleotide polymorphism rs11218343 is linked to functional expression of SORL1 in microglia.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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.
Gorniak-Walas Malgorzata, Telugu Narasimha S, Rudolph Ina-Maria, Diecke Sebastian, Willnow Thomas E
Аннотация
INTRODUCTION: The rs11218343 is a non-coding variant of genome-wide significance for sporadic Alzheimer's disease (AD) with one of the most protective effects known to date. It localizes to SORL1, encoding the AD risk factor Sortilin-related receptor with A type repeats (SORLA). Still, the functional significance of rs11218343 for AD-related processes remains unclear.
METHODS: We used induced pluripotent stem cell (iPSC) lines from donors, or genome-engineered to carry major and minor rs11218343 alleles, to study the impact of rs11218343 on cellular activities.
RESULTS: We show that rs11218343 is uniquely linked to functional expression of SORLA in microglia, with increased expression in the protective allele correlating with reduced pro-inflammatory responses. These anti-inflammatory effects are seen in donor lines but not in single nucleotide polymorphism (SNP) -engineered isogenic lines, arguing that this polymorphism alone is insufficient but acting context-dependent.
DISCUSSION: Our data infer genetically defined expression of SORL1 in microglia as a determinant of protection from pro-inflammatory stimulation, a function likely encoded by a haplotype linked to rs11218343.
METHODS: We used induced pluripotent stem cell (iPSC) lines from donors, or genome-engineered to carry major and minor rs11218343 alleles, to study the impact of rs11218343 on cellular activities.
RESULTS: We show that rs11218343 is uniquely linked to functional expression of SORLA in microglia, with increased expression in the protective allele correlating with reduced pro-inflammatory responses. These anti-inflammatory effects are seen in donor lines but not in single nucleotide polymorphism (SNP) -engineered isogenic lines, arguing that this polymorphism alone is insufficient but acting context-dependent.
DISCUSSION: Our data infer genetically defined expression of SORL1 in microglia as a determinant of protection from pro-inflammatory stimulation, a function likely encoded by a haplotype linked to rs11218343.