Locus coeruleus intensity as a marker of early-stage Alzheimers disease: associations with plasma pTau217 and memory
- 1University of Southern California
Abstract
INTRODUCTIONThe locus coeruleus (LC) is one of the earliest sites of Alzheimers 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 (pTau217), and memory in older adults without dementia.
METHODSIndependently 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 pTau217 was measured using the Quanterix ALZpath p-Tau217 Advantage PLUS assay. For a subset (n = 127), a memory composite score was calculated.
RESULTSAfter adjustment for age, sex, and APOE {varepsilon}4 status, lower LC intensity was associated with higher plasma pTau217 concentrations ({beta} = -0.17, P = .02). Each 1-SD decrease in LC intensity was associated with 53% higher odds of pTau217 positivity (P = .03). In models additionally adjusted for education, a significant LC x pTau217 interaction for memory ({beta} = -0.18, P = .009) indicated that lower LC intensity was associated with worse memory at low (P = .01), but not high (P = .64) pTau217 levels.
DISCUSSIONThese 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 pTau217 alone. Longitudinal studies are warranted to determine how these relationships change across the early stages of AD.
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BibTeX
@misc{quiring2026locus,
title = {{Locus coeruleus intensity as a marker of early-stage Alzheimers disease: associations with plasma pTau217 and memory}},
author = {M. Quiring and Y. Shuai and W. Zhao and J. P. Alitin and A. Kapoor and A. C. Engstrom and J. L. Joyce and P. Iyengar and T. Lohman and B. Lashin and A. Gaubert and F. Shenasa and L. Contreras and K. W. Law and F. Ferrer and D. J. Wang and E. Head and R. Malhas and K. Rodgers and S. D. Han and J. F. Thayer and M. W. Bondi and D. A. Nation},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.26364896},
url = {https://www.medrxiv.org/content/10.64898/2026.10.07.26364896v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Locus coeruleus intensity as a marker of early-stage Alzheimers disease: associations with plasma pTau217 and memory
AU - M. Quiring
AU - Y. Shuai
AU - W. Zhao
AU - J. P. Alitin
AU - A. Kapoor
AU - A. C. Engstrom
AU - J. L. Joyce
AU - P. Iyengar
AU - T. Lohman
AU - B. Lashin
AU - A. Gaubert
AU - F. Shenasa
AU - L. Contreras
AU - K. W. Law
AU - F. Ferrer
AU - D. J. Wang
AU - E. Head
AU - R. Malhas
AU - K. Rodgers
AU - S. D. Han
AU - J. F. Thayer
AU - M. W. Bondi
AU - D. A. Nation
PY - 2026
DA - 2026/10/07
PB - medRxiv
DO - 10.64898/2026.10.07.26364896
UR - https://www.medrxiv.org/content/10.64898/2026.10.07.26364896v1
AB - INTRODUCTIONThe locus coeruleus (LC) is one of the earliest sites of Alzheimers 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 (pTau217), and memory in older adults without dementia. METHODSIndependently 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 pTau217 was measured using the Quanterix ALZpath p-Tau217 Advantage PLUS assay. For a subset (n = 127), a memory composite score was calculated. RESULTSAfter adjustment for age, sex, and APOE {varepsilon}4 status, lower LC intensity was associated with higher plasma pTau217 concentrations ({beta} = -0.17, P = .02). Each 1-SD decrease in LC intensity was associated with 53% higher odds of pTau217 positivity (P = .03). In models additionally adjusted for education, a significant LC x pTau217 interaction for memory ({beta} = -0.18, P = .009) indicated that lower LC intensity was associated with worse memory at low (P = .01), but not high (P = .64) pTau217 levels. DISCUSSIONThese 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 pTau217 alone. Longitudinal studies are warranted to determine how these relationships change across the early stages of AD.
ER -