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. 2024 Jan;20(1):356-365.
doi: 10.1002/alz.13407. Epub 2023 Aug 25.

The heritability of blood-based biomarkers related to risk of Alzheimer's disease in a population-based sample of early old-age men

Nathan A Gillespie  1   2 , Jeremy A Elman  3   4 , Ruth E McKenzie  5   6 , Xin M Tu  4   7 , Hong Xian  8   9 , Chandra A Reynolds  10 , Matthew S Panizzon  3   4 , Michael J Lyons  11 , Graham M L Eglit  3   12 , Michael C Neale  1 , Robert A Rissman  3   4 , Carol Franz  3   4 , William S Kremen  3   4   13
Affiliations

The heritability of blood-based biomarkers related to risk of Alzheimer's disease in a population-based sample of early old-age men

Nathan A Gillespie et al. Alzheimers Dement. 2024 Jan.

Abstract

Introduction: Despite their increased application, the heritability of Alzheimer's disease (AD)-related blood-based biomarkers remains unexplored.

Methods: Plasma amyloid beta 40 (Aβ40), Aβ42, the Aβ42/40 ratio, total tau (t-tau), and neurofilament light (NfL) data came from 1035 men 60 to 73 years of age (μ = 67.0, SD = 2.6). Twin models were used to calculate heritability and the genetic and environmental correlations between them.

Results: Additive genetics explained 44% to 52% of Aβ42, Aβ40, t-tau, and NfL. The Aβ42/40 ratio was not heritable. Aβ40 and Aβ42 were genetically near identical (rg = 0.94). Both Aβ40 and Aβ42 were genetically correlated with NfL (rg = 0.35 to 0.38), but genetically unrelated to t-tau.

Discussion: Except for Aβ42/40, plasma biomarkers are heritable. Aβ40 and Aβ42 share mostly the same genetic influences, whereas genetic influences on plasma t-tau and NfL are largely unique in early old-age men. The absence of genetic associations between the Aβs and t-tau is not consistent with the amyloid cascade hypothesis.

Keywords: Aβ40; Aβ42; Aβ42/40 ratio; gene; heritability; neurofilament light (NfL); plasma biomarkers; total tau (t-tau); twin.

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Conflict of interest statement

The authors have no conflict of interest to report. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Univariate variance decomposition to estimate the relative contribution of additive genetic (A), common (C), and non‐shared (E) environmental influences in each biomarker.
FIGURE 2
FIGURE 2
Multivariate correlated factors model to estimate the sources of genetic and environmental variances and covariances between the Aβ40, Aβ42, t‐tau, and neurofilament light (NfL) biomarkers.
See this image and copyright information in PMC

References

    1. 2020 Alzheimer's disease facts and figures. Alzheimers Dement. 2020. - PubMed
    1. Collaborators., U.B.o.D. , The state of US health, 1990‐2010: burden of diseases, injuries, and risk factors. JAMA. 2013;310(6):591‐608. - PMC - PubMed
    1. Daviglus ML, Bell CC, Berrettini W, et al. In NIH Consensus Statement Science Statements. National Institutes of Health State‐of‐the‐Science Conference statement: Preventing Alzherimer's disease and cognitive decline; 2010:1‐27. - PubMed
    1. Albert MS, Dekosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270‐279. - PMC - PubMed
    1. Sperling RA, Jack CR, Aisen PS. Testing the right target and right drug at the right stage. Sci Transl Med. 2011;3(111):111cm33. - PMC - PubMed

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