Association of plasma biomarkers with longitudinal change in age- and Alzheimer's disease-related brain atrophy patterns
- 1National Institute on Aging
Abstract
INTRODUCTIONDetermining whether plasma biomarkers are preferentially associated with Alzheimers disease (AD)-related rather than age-related brain atrophy patterns may clarify their prognostic and diagnostic clinical use.
METHODSUsing data from the Baltimore Longitudinal Study of Aging (N=818), we examined cross-sectional plasma A{beta}42/A{beta}40, GFAP, NfL, p-tau181, and p-tau217 measurements obtained while participants were cognitively unimpaired (CU). During follow-up, 104 participants developed mild cognitive impairment (MCI)/dementia (74 due to AD, 24 due to non-AD, 6 unknown etiology). 2,293 longitudinal brain MRIs were used to quantify multidimensional atrophy pattern scores reflecting brain age (SPARE-BA), AD-like patterns (SPARE-AD), and five dominant dimensions of atrophy (R-indices). We investigated the associations of plasma biomarkers and atrophy pattern scores at index visit with conversion to MCI/dementia due to AD. We then examined the associations of plasma biomarkers with longitudinal change in pattern scores using linear mixed effects models.
RESULTSp-tau181, A{beta}42/A{beta}40 (Lumipulse), and p-tau217 were associated with incident MCI/dementia due to AD but not non-AD etiologies, while GFAP was associated with incident MCI/dementia due to both AD and non-AD. All four biomarkers were associated with longitudinal SPARE-AD changes. A{beta}42/A{beta}40 (Quanterix and Lumipulse), p-tau181, and p-tau217 were associated with longitudinal parieto-temporal atrophy. p-tau217 was the only biomarker associated with longitudinal medial temporal lobe atrophy. We did not find associations between plasma biomarkers and SPARE-BA or R-indices capturing subcortical, diffuse cortical, or perisylvian atrophy.
DISCUSSIONAmong CU individuals, plasma p-tau217 was associated with subsequent MCI/dementia due to AD and showed the most extensive associations with longitudinal AD-related brain atrophy.
Related
- Case Report: Longitudinal evaluation of cerebrospinal fluid Alzheimer’s disease core biomarkers in a case of refractory late-onset epilepsy of unknown etiology
- Location-specific Longitudinal Patterns of Subcortical and Lobar Cerebral Microhemorrhages in Preclinical Alzheimer Disease
- A neurocognitive speech taxonomy for voice biomarkers of Alzheimer's disease
- CSF Alzheimer's Disease Biomarkers in Relation to Functional Status and Tofersen Treatment Response in ALS
- Global research trends and hotspots in blood-based biomarkers for Alzheimer’s disease: a bibliometric analysis
BibTeX
@misc{bilgel2026association,
title = {{Association of plasma biomarkers with longitudinal change in age- and Alzheimer's disease-related brain atrophy patterns}},
author = {M. Bilgel and I. Shah and J. Cooper and Y. An and K. A. Walker and S. G. Ho and A. R. Moghekar and Z. Yang and G. Erus and C. Davatzikos and L. Ferrucci and S. M. Resnick},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.26362869},
url = {https://www.medrxiv.org/content/10.64898/2026.09.11.26362869v1},
note = {CC0},
}
RIS
TY - UNPB
TI - Association of plasma biomarkers with longitudinal change in age- and Alzheimer's disease-related brain atrophy patterns
AU - M. Bilgel
AU - I. Shah
AU - J. Cooper
AU - Y. An
AU - K. A. Walker
AU - S. G. Ho
AU - A. R. Moghekar
AU - Z. Yang
AU - G. Erus
AU - C. Davatzikos
AU - L. Ferrucci
AU - S. M. Resnick
PY - 2026
DA - 2026/09/11
PB - medRxiv
DO - 10.64898/2026.09.11.26362869
UR - https://www.medrxiv.org/content/10.64898/2026.09.11.26362869v1
AB - INTRODUCTIONDetermining whether plasma biomarkers are preferentially associated with Alzheimers disease (AD)-related rather than age-related brain atrophy patterns may clarify their prognostic and diagnostic clinical use. METHODSUsing data from the Baltimore Longitudinal Study of Aging (N=818), we examined cross-sectional plasma A{beta}42/A{beta}40, GFAP, NfL, p-tau181, and p-tau217 measurements obtained while participants were cognitively unimpaired (CU). During follow-up, 104 participants developed mild cognitive impairment (MCI)/dementia (74 due to AD, 24 due to non-AD, 6 unknown etiology). 2,293 longitudinal brain MRIs were used to quantify multidimensional atrophy pattern scores reflecting brain age (SPARE-BA), AD-like patterns (SPARE-AD), and five dominant dimensions of atrophy (R-indices). We investigated the associations of plasma biomarkers and atrophy pattern scores at index visit with conversion to MCI/dementia due to AD. We then examined the associations of plasma biomarkers with longitudinal change in pattern scores using linear mixed effects models. RESULTSp-tau181, A{beta}42/A{beta}40 (Lumipulse), and p-tau217 were associated with incident MCI/dementia due to AD but not non-AD etiologies, while GFAP was associated with incident MCI/dementia due to both AD and non-AD. All four biomarkers were associated with longitudinal SPARE-AD changes. A{beta}42/A{beta}40 (Quanterix and Lumipulse), p-tau181, and p-tau217 were associated with longitudinal parieto-temporal atrophy. p-tau217 was the only biomarker associated with longitudinal medial temporal lobe atrophy. We did not find associations between plasma biomarkers and SPARE-BA or R-indices capturing subcortical, diffuse cortical, or perisylvian atrophy. DISCUSSIONAmong CU individuals, plasma p-tau217 was associated with subsequent MCI/dementia due to AD and showed the most extensive associations with longitudinal AD-related brain atrophy.
ER -