Plasma pTau181 is associated with subjective cognitive concerns but not objective cognitive decline or structural brain integrity measures in midlife
AI Summary
Plasma pTau181 at age 45 associated with self-reported cognitive concerns (β = 0.09, p = .008).
No significant associations between plasma pTau181 and objective cognitive decline, structural brain integrity, or epigenetic biological ageing (DunedinPACE).
Findings suggest Alzheimer's disease pathology may begin accumulating by age 45, producing subtle subjective changes not detectable by objective measures.
Geroscience. 2026 May 8. doi: 10.1007/s11357-026-02282-z. Online ahead of print.
ABSTRACT
Although plasma pTau181 has been shown to accurately discriminate patients with Alzheimer’s disease from healthy older adults, there are few studies of plasma biomarkers among middle-aged populations. Given the potential utility of plasma AD biomarkers such as pTau181 in screening for disease risk, examining pTau181 in a middle-aged cohort without AD is important for future implementation. The objectives of this study were to characterise plasma pTau181 in a middle-aged birth cohort aged 45 years and to investigate associations with early indicators of dementia risk. Participants were members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal study of 1037 people born in New Zealand in 1972-1973. Plasma pTau181, self-reported cognitive concerns, MRI-based brain structure, and DunedinPACE (an epigenetic biomarker of biological ageing) were measured at age 45; cognition was measured in childhood and age 45. Plasma pTau181 concentrations at age 45 (n = 854, 49% female) were associated with self-reported cognitive concerns (β = 0.09, p = .008); however, no significant associations were observed with objective cognitive decline, worse structural brain integrity, or biological ageing. Higher plasma pTau181 was associated with self-reported cognitive concerns at age 45, but not objective AD-related measures. The association of plasma pTau181 and self-reported cognitive concerns in this cohort suggests that AD pathology may begin to accumulate by age 45 and may be associated with subtle changes in cognition that are not at objectively measurable levels.
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