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.