Heritability of Alzheimer-related plasma biomarkers in the Amish population

Plasma biomarkers for Alzheimer disease (AD) hold promise for disease diagnosis and prediction, yet their genetic underpinnings remain underexplored.

We measured plasma amyloid beta 40 (Aβ40), Aβ42, Aβ42/Aβ40, total tau (t-tau), phosphorylated tau 181 (p-tau181), Aβ42/t-tau, Aβ42/p-tau181, neurofilament light chain, and glial fibrillary acidic protein in the Midwestern Amish. Pedigree-based heritability was estimated from multigenerational pedigrees, and SNP-based heritability was derived from single nucleotide polymorphisms (SNPs).

Among all Amish individuals, additive genetic effects explained 11.1% to 36.6% of biomarker variances. estimates were consistently lower, ranging from 6.7% to 28.7%. The heritability of these biomarkers in subgroups of cognitively normal individuals and APOE ε4 non-carriers yielded similar results.

Plasma biomarkers such as amyloid β, t-tau, and p-tau181 are moderately heritable in the Amish, underscoring the impact of genetic determinants of plasma biomarkers associated with AD. Competing Interest Statement The authors have declared no competing interest. Funding Statement This research was funded by the National Institutes of Health and National Institute on Aging (grants AG019085, AG019726, and AG058066). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of Case Western Reserve University and the University of Miami gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes I identified a typo in the manuscript after submission, this revision is to correct it. Data Availability All data produced in the present study are available upon reasonable request to the authors.