Work

Locus coeruleus intensity as a marker of early-stage Alzheimer’s disease: associations with plasma pTau 217 and memory

Year: 2026

Type: preprint

Abstract: ABSTRACT INTRODUCTION The locus coeruleus (LC) is one of the earliest sites of Alzheimer’s disease (AD) pathophysiological changes. LC magnetic resonance imaging (MRI) intensity may reflect effects of AD pathophysiology on the LC, providing a biomarker of early-stage AD. This study examined relationships among MRI-derived LC intensity, plasma phosphorylated tau 217 (pTau 217 ), and memory in older adults without dementia. METHODS Independently living adults aged 59–89 years ( N = 163) underwent neuropsychological assessment and T1-weighted fast spin-echo MRI. We quantified a bilateral LC contrast ratio relative to a pontine reference region, averaged across axial slices. Plasma pTau 217 was measured using the Quanterix ALZpath p-Tau217 Advantage PLUS assay. For a subset ( n = 127), a memory composite score was calculated. RESULTS After adjustment for age, sex, and APOE ɛ4 status, lower LC intensity was associated with higher plasma pTau 217 concentrations (β = −0.17, P = .02). Each 1- SD decrease in LC intensity was associated with 53% higher odds of pTau 217 positivity ( P = .03). In models additionally adjusted for education, a significant LC × pTau 217 interaction for memory (β = −0.18, P = .009) indicated that lower LC intensity was associated with worse memory at low ( P = .01), but not high ( P = .64) pTau 217 levels. DISCUSSION These findings support MRI-derived LC intensity as a marker of early AD-related processes and suggest that LC intensity may provide complementary information not captured by plasma pTau 217 alone. Longitudinal studies are warranted to determine how these relationships change across the early stages of AD.

Source: medRxiv

DOI: 10.64898/2026.10.07.26364896