{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:27:09Z","timestamp":1785403629489,"version":"3.56.0"},"reference-count":43,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,12,6]]},"abstract":"<jats:p>Background: APOE \u025b4 and PICALM are established genes associated with risk of late-onset Alzheimer\u2019s disease (AD). Previous study indicated interaction of PICALM with APOE \u025b4 in AD patients. Objective: To explore whether PICALM variation could moderate the influences of APOE \u025b4 on AD pathology biomarkers and cognition in pre-dementia stage. Methods: A total of 1,034 non-demented participants (mean age 74 years, 56% females, 40% APOE \u025b4 carriers) were genotyped for PICALM rs3851179 and APOE \u025b4 at baseline and were followed for influences on changes of cognition and cerebrospinal fluid (CSF) AD markers in six years. The interaction effects were examined via regression models adjusting for age, gender, education, and cognitive diagnosis. Results: The interaction term of rs3851179\u00d7APOE \u025b4 accounted for a significant amount of variance in baseline general cognition (p\u200a=\u200a0.039) and memory function (p\u200a=\u200a0.002). The relationships of APOE \u025b4 with trajectory of CSF A\u03b242 (p\u200a=\u200a0.007), CSF P-tau181 (p\u200a=\u200a0.003), CSF T-tau (p\u200a=\u200a0.001), and memory function (p\u200a=\u200a0.017) were also moderated by rs3851179 variation. Conclusions: APOE \u025b4 carriers experienced slower clinical and pathological progression when they had more protective A alleles of PICALM rs3851179. These findings firstly revealed the gene-gene interactive effects of PICALM with APOE \u025b4 in pre-dementia stage.<\/jats:p>","DOI":"10.3233\/jad-230516","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T11:32:21Z","timestamp":1700566341000},"page":"1651-1661","source":"Crossref","is-referenced-by-count":4,"title":["PICALM Variation Moderates the Relationships of APOE \u025b4 with Alzheimer\u2019s Disease Cerebrospinal Biomarkers and Memory Function Among Non-Demented Population"],"prefix":"10.1177","volume":"96","author":[{"given":"Yan-Bing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"},{"name":"Medical college, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Chen","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, 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