ArticlemedRxiv : the preprint server for health sciences2026
Behavioral and psychological symptoms of dementia: insights from a multivariate and network-based brain proteome-wide study.
Article in medRxiv : the preprint server for health sciences, 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
Behavioral and psychological symptoms of dementia (BPSD) are common, profoundly troubling to patients and caregivers, and difficult to treat, yet their molecular underpinnings remain poorly understood. Here, we generated a large brain proteomic dataset with nine BPSD domains assessed in life from 376 donors from three cohorts. Protein associations with BPSD were examined using complementary approaches - domain-specific BPSD, multi-domain BPSD, and latent factor modeling - and integrated via cross-cohort meta-analysis. Four proteins (NMT1, DCAKD, DNPH1, and HIBADH) were associated with anxiety in dementia and five proteins (ABL1, SAP18, PLXND1, CTRB2, and LDHD) with multi-domain BPSD or BPSD latent factors after adjusting for sex, age, and other covariates (FDR < 0.05). Additionally, eight protein co-expression networks were associated with BPSD across cohorts. Together, these results link BPSD to dysregulation of synaptic signaling, protein folding, and humoral immune response, providing a molecular framework for therapeutic discovery.
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