Abstract
Background
The diagnostic value of blood-based biomarkers for Alzheimer's disease (AD) neuropathology has been demonstrated in individuals with cognitive impairment; however, evidence for reliable preclinical stage diagnostic methods remains insufficient.
Objective
To identify confounding variables that may obscure the interpretation of these biomarkers, we examined their associations with various physiological indices including age, renal function, and cognitive function in Japanese men from the general population.
Methods
Plasma were collected from 845 randomly selected Japanese men participants (aged >40 years) to measure 40- and 42-amino acid amyloid-β (Aβ40 and Aβ42), total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and neurofilament light chain (NfL) using an automated immunoassay system. Cognitive function was assessed using the Cognitive Abilities Screening Instrument (CASI). Linear regression models were constructed to estimate association strengths with correction for possible confounding variables.
Results
Plasma Aβ40, Aβ42, T-tau, P-tau181, NfL, and P-tau181/T-tau increased with age and declining glomerular filtration rate (eGFR), whereas Aβ42/Aβ40 decreased with age. Higher T-tau and P-tau181 were associated with lower CASI scores after adjusting for age and eGFR. Individuals in older age groups with Aβ42/Aβ40 ratios less than or equal to a cutoff (“amyloid-positive”) also exhibited higher P-tau181, NfL, and P-tau181/T-tau than amyloid-negative individuals, with no significant difference in mean CASI score.
Conclusions
Our results confirm that plasma AD biomarkers are significantly influenced by age and renal clearance rate. Notably, higher T-tau and P-tau181 were associated with preclinical cognitive impairment. Additionally, a lower Aβ42/Aβ40 was associated with asymptomatic tau pathology and neurodegeneration.
Get full access to this article
View all access options for this article.
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
