{"doi":"10.1002/alz.13862","title":"CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease","abstract":"INTRODUCTION: We examined whether baseline glial markers soluble triggering receptor expressed on myeloid cell 2 (sTREM2), chitinase 3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF), and plasma GFAP are associated with cognitive change in cognitively unimpaired (CU) individuals at risk of Alzheimer's disease (AD). METHODS: A total of 353 CU (mean age 60.9 years) participants were included (mean follow-up time 3.28 years). Linear regression models with cognition as outcome were used. We also tested whether amyloid beta (Aβ) status modified these associations. RESULTS: Higher baseline CSF sTREM2 was associated with a positive global cognition (Preclinical Alzheimer's Cognitive Composite) rate of change, and better memory and executive outcomes, independently of AD pathology. Higher baseline plasma GFAP was associated with a decline on attention rate of change. Stratified analyses by Aβ status showed that CSF sTREM2 and YKL-40 were positively associated with executive functioning in amyloid negative (Aβ-) individuals. DISCUSSION: Our results suggest that a TREM2-mediated microglial response may be associated with better longitudinal cognitive performance. HIGHLIGHTS: Higher cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cell 2 (sTREM2) relates to better longitudinal cognitive performance. The association between CSF sTREM2 and cognition is independent of Alzheimer's disease (AD) pathology. Targeting microglial reactivity may be a therapeutic strategy for AD prevention.","journal":"Alzheimer s & Dementia","year":2024,"id":430785,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9038,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":654908,"name":"Gonzalo Sánchez‐Benavides","orcid":"0000-0003-3454-800X","position":1,"is_corresponding":false},{"id":839825,"name":"Armand González‐Escalante","orcid":"0000-0001-9456-5405","position":2,"is_corresponding":false},{"id":658015,"name":"Marta Milà‐Alomà","orcid":"0000-0002-5687-4597","position":3,"is_corresponding":false},{"id":1234119,"name":"Mahnaz Shekari","orcid":"0000-0003-0531-8651","position":4,"is_corresponding":false},{"id":1234120,"name":"David López‐Martos","orcid":"0009-0008-1150-2619","position":5,"is_corresponding":false},{"id":839824,"name":"Paula Ortiz‐Romero","orcid":"0000-0002-6378-6763","position":6,"is_corresponding":false},{"id":671639,"name":"Gwendlyn Kollmorgen","orcid":null,"position":7,"is_corresponding":false},{"id":1234121,"name":"Clara Quijano‐Rubio","orcid":"0000-0001-9050-3282","position":8,"is_corresponding":false},{"id":635121,"name":"Carolina Minguillón","orcid":"0000-0002-2782-6908","position":9,"is_corresponding":false},{"id":518200,"name":"Juan Domingo Gispert","orcid":"0000-0002-6155-0642","position":10,"is_corresponding":false},{"id":241461,"name":"Natàlia Vilor‐Tejedor","orcid":"0000-0003-4935-6721","position":11,"is_corresponding":false},{"id":291747,"name":"Eider M. 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