Genetic Architecture of Plasma Amyloid and Tau Biomarkers in the Amish
- 1Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
Abstract
BackgroundPlasma biomarkers offer a minimally invasive alternative for detecting Alzheimers disease (AD) pathology, yet the genetic determinants influencing their levels remain largely underexplored.
ObjectiveTo identify genetic variants associated with AD-related plasma biomarker levels in a Midwestern Amish cohort.
MethodsWe analyzed plasma levels of amyloid beta (A{beta}42/A{beta}40), phosphorylated tau 181 (p-tau181), and the p-tau181/A{beta}42 ratio in the Midwestern Amish. Genome-wide association studies (GWAS) were used to examine associations with common genetic variants, while genetic linkage analysis was used to assess the potential impact of rare variants.
ResultsGWAS found associations between plasma biomarkers and the APOE gene. Additionally, novel candidate genes were implicated, including MME for A{beta}42/A{beta}40 ratio, and VEGFC and LRRTM4 for p-tau181. Linkage analysis identified significant signals for p-tau181 on chromosome 1, potentially involving the CSF1 and AHCYL1 genes.
ConclusionsThe novel genetic variants associated with AD pathology implicate metabolic, synaptic, neuronal, and immune pathways. The use of GWAS and linkage analysis sheds light on the genetic architecture of AD-related plasma biomarkers.
Related
- Cerebrospinal fluid amyloid and neurodegeneration biomarkers in the diagnosis and prognosis of amyotrophic lateral sclerosis: a multicohort observational study
- Amyloid-Independent Elevation of Plasma phosphorylated tau-217 Tracks Neurodegenerative Risk in Tuberous Sclerosis Complex: Implications for mTOR-Targeted Intervention
- Stage-Specific Roles of Plasma GFAP in Linking Amyloid Cascade in Alzheimer Disease
- Cross‐cohort NULISAseq identifies tau‐anchored CSF and plasma‐specific signatures across the amyloid‐positive Alzheimer's disease
- Analytical validation and amyloid-status discrimination of a high-throughput, research-use-only plasma p-Tau217 immunoassay
BibTeX
@misc{wang2026genetic,
title = {{Genetic Architecture of Plasma Amyloid and Tau Biomarkers in the Amish}},
author = {P. Wang and D. Z. Jian and Y. E. Song and A. Lynn and K. Miskimen and P. G. Whitehead and A. V. Gulyayev and M. B. Prough and D. A. Dorfsman and R. A. Laux and S. L. Fuzzell and D. Miller and S. D. Hochstetler and P. Miron and A. F. Zaman and L. D. Adams and L. J. Caywood and J. E. Clouse and S. D. Herington and Y. Liu and N. C. Moore and P. Ogrocki and A. J. Lerner and A. J. Griswold and M. L. Cuccaro and J. M. Vance and W. K. Scott and M. A. Pericak-Vance and J. L. Haines},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.15.26365636},
url = {https://www.medrxiv.org/content/10.64898/2026.10.15.26365636v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Genetic Architecture of Plasma Amyloid and Tau Biomarkers in the Amish
AU - P. Wang
AU - D. Z. Jian
AU - Y. E. Song
AU - A. Lynn
AU - K. Miskimen
AU - P. G. Whitehead
AU - A. V. Gulyayev
AU - M. B. Prough
AU - D. A. Dorfsman
AU - R. A. Laux
AU - S. L. Fuzzell
AU - D. Miller
AU - S. D. Hochstetler
AU - P. Miron
AU - A. F. Zaman
AU - L. D. Adams
AU - L. J. Caywood
AU - J. E. Clouse
AU - S. D. Herington
AU - Y. Liu
AU - N. C. Moore
AU - P. Ogrocki
AU - A. J. Lerner
AU - A. J. Griswold
AU - M. L. Cuccaro
AU - J. M. Vance
AU - W. K. Scott
AU - M. A. Pericak-Vance
AU - J. L. Haines
PY - 2026
DA - 2026/10/15
PB - medRxiv
DO - 10.64898/2026.10.15.26365636
UR - https://www.medrxiv.org/content/10.64898/2026.10.15.26365636v1
AB - BackgroundPlasma biomarkers offer a minimally invasive alternative for detecting Alzheimers disease (AD) pathology, yet the genetic determinants influencing their levels remain largely underexplored. ObjectiveTo identify genetic variants associated with AD-related plasma biomarker levels in a Midwestern Amish cohort. MethodsWe analyzed plasma levels of amyloid beta (A{beta}42/A{beta}40), phosphorylated tau 181 (p-tau181), and the p-tau181/A{beta}42 ratio in the Midwestern Amish. Genome-wide association studies (GWAS) were used to examine associations with common genetic variants, while genetic linkage analysis was used to assess the potential impact of rare variants. ResultsGWAS found associations between plasma biomarkers and the APOE gene. Additionally, novel candidate genes were implicated, including MME for A{beta}42/A{beta}40 ratio, and VEGFC and LRRTM4 for p-tau181. Linkage analysis identified significant signals for p-tau181 on chromosome 1, potentially involving the CSF1 and AHCYL1 genes. ConclusionsThe novel genetic variants associated with AD pathology implicate metabolic, synaptic, neuronal, and immune pathways. The use of GWAS and linkage analysis sheds light on the genetic architecture of AD-related plasma biomarkers.
ER -