Year: 2024
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Alzheimer's disease (AD) is a highly heritable disease (60%-80%). Amyloid beta (Aβ) 42/40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) are plasma biomarkers for AD. Clinical biomarker research would be served by an understanding of the sources of variance in these markers. METHODS: Blood concentrations of Aβ42/40, NfL, and GFAP of twins and their families (monozygotic twins: 1574, dizygotic twins: 1266, other: 3657) were analyzed on the Simoa HD-X. Twin-family models were used to estimate proportional genetic contributions to the variance in biomarker levels. RESULTS: Heritability estimates were 16% for Aβ42/40, 42% for NfL, and 60% for GFAP. NfL and GFAP were significantly correlated with each other (0.37) but not with Aβ42/40. DISCUSSION: The heritability of Aβ42/40 (16%) is lower than the heritability of AD, suggesting strong environmental influences on this biomarker. The lack of correlation between NfL/GFAP and Aβ42/40 indicates these markers may be on different biological pathways. HIGHLIGHTS: Heritability is found for glial fibrillary acidic protein (60%), neurofilament light chain (42%), and amyloid beta (Aβ) 42/40 (16%) plasma levels. Aβ42/40 plasma levels are sensitive to person-specific environmental influences.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.14269
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
Funders: National Multiple Sclerosis Society, Alzheimer's Association, EU Joint Programme – Neurodegenerative Disease Research, International Progressive MS Alliance, Multiple Sclerosis Society, European Commission, ZonMw, Vrije Universiteit Amsterdam, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Alzheimer Nederland, Selfridges Group Foundation, FP7 Health
Awards: G1108774313, G1110999434, G1311351439, G1409398652, G1613806636, G178382592, G1798618210, G2172067207, G2238725043, G2501976640, G2563833389, G3077543175, G3194766268, G3207356259, G323630742, G3381003921, European platform for neurodegenerative disorders, Identification of the Molecular Mechanisms of non-response to Treatments, Relapses and Remission in Autoimmune, Inflammatory, and Allergic Conditions, G434337789, G4367295956, G4599390081, G4757721458, G5092714882, G5418186242, G5471839915, G5598020036, G5616778589, G5802200490, G5929196451, G6091493096, G626177176, G634521393, G663896020, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6728033037, G70080636, Netherlands Twin Registry Repository: researching the interplay between genome and environment, G7461077622, G7780068114, G7843020198, G822877548, G84497985, G8547141348, G947884680
OpenAlex ID: W4404719775