ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026
Alzheimer's disease risk single nucleotide polymorphism rs11218343 is linked to functional expression of SORL1 in microglia.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionThe 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.
methodsWe 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.
resultsWe 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.
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