{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tsui JSM"],"funding":["Research Grants Council of Hong Kong (General Research Fund)","Chow Tai Fook Charity Foundation","SIAT-HKUST Joint Laboratory for Brain Science","InnoHK Initiative and Grant of the Innovation and Technology Commission of the HKSAR Government","NSFC-RGC Joint Research Scheme","Research Grants Council of Hong Kong (Theme-Based Research Scheme)","Research Grants Council of Hong Kong (Collaborative Research Fund)","Area of Excellence Scheme of the University Grants Committee"],"pagination":["e70586"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12441928"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["21(9)"],"pubmed_abstract":["<h4>Introduction</h4>Multiple TREM2 variants are associated with an increased risk of Alzheimer's disease (AD). TREM2 H157Y is the only variant located at the proteolytic cleavage site that enhances TREM2 protein shedding. While this variant is associated with increased AD risk predominantly in the Chinese population, its impact on AD pathology is largely unknown.<h4>Methods</h4>We conducted an in-depth study integrating clinical cases, neuroimaging data, and blood proteomic data.<h4>Results</h4>TREM2 H157Y variant carriers with AD exhibit more severe AD pathology, more severe neurodegeneration, and more rapid clinical progression. Cognitively normal individuals carrying the variant show changes in blood proteins that are associated with neurodegeneration and inflammation. Moreover, the TR"],"journal":["Alzheimer's & dementia : the journal of the Alzheimer's Association"],"pubmed_title":["The TREM2 H157Y variant is associated with more severe neurodegeneration in Alzheimer's disease and altered immune-related processes."],"pmcid":["PMC12441928"],"funding_grant_id":["C6027-19GF","HKUST16102824","CTFCF18SC01","AoE/M-604/16","ITCPD/17-9","HKUST16103122","32061160472","JLFS/M-604/24","T13-605/18W"],"pubmed_authors":["Jiang Y","Wong HY","Mok KY","Kwok TCY","Tsui JSM","Wong WW","Lo RMN","Ip FCF","Au DM","Uhm H","Ip NY","Fu AKY"],"additional_accession":[]},"is_claimable":false,"name":"The TREM2 H157Y variant is associated with more severe neurodegeneration in Alzheimer's disease and altered immune-related processes.","description":"<h4>Introduction</h4>Multiple TREM2 variants are associated with an increased risk of Alzheimer's disease (AD). TREM2 H157Y is the only variant located at the proteolytic cleavage site that enhances TREM2 protein shedding. While this variant is associated with increased AD risk predominantly in the Chinese population, its impact on AD pathology is largely unknown.<h4>Methods</h4>We conducted an in-depth study integrating clinical cases, neuroimaging data, and blood proteomic data.<h4>Results</h4>TREM2 H157Y variant carriers with AD exhibit more severe AD pathology, more severe neurodegeneration, and more rapid clinical progression. Cognitively normal individuals carrying the variant show changes in blood proteins that are associated with neurodegeneration and inflammation. Moreover, the TR","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T11:21:57.454Z","creation":"2026-05-29T03:06:15.718Z"},"accession":"S-EPMC12441928","cross_references":{"pubmed":["40960087"],"doi":["10.1002/alz.70586"]}}