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Association of plasma Alzheimer's disease biomarkers with cognitive decline in cognitively unimpaired individuals

Cogswell, Petrice M. ; Wiste, Heather J. ; Therneau, Terry M. ; Griswold, Michael E. ; Mattsson-Carlgren, Niklas LU orcid ; Palmqvist, Sebastian LU orcid ; Binette, Alexa Pichet LU ; Stomrud, Erik LU orcid ; Bateman, Randall J. and Barthelemy, Nicolas , et al. (2025) In Alzheimer's and Dementia 21(9).
Abstract

INTRODUCTION: Plasma biomarkers’ utility for predicting incident mild cognitive impairment (MCI) remains unclear. We evaluated associations of plasma Alzheimer's disease (AD) biomarkers and amyloid positron emission tomography (PET) with transitions from cognitively unimpaired (CU) to MCI in the Mayo Clinic Study of Aging (MCSA) and BioFINDER-2 studies. METHODS: Associations of continuous baseline plasma biomarker levels and amyloid PET Centiloid with progression to MCI, adjusting for age, sex, and education, were evaluated with Cox proportional hazards models. RESULTS: The study included 381 MCSA and 584 BioFINDER-2 participants. Amyloid PET and percent phosphorylated to non-phosphorylated tau217 (%p-tau217) were strong predictors of... (More)

INTRODUCTION: Plasma biomarkers’ utility for predicting incident mild cognitive impairment (MCI) remains unclear. We evaluated associations of plasma Alzheimer's disease (AD) biomarkers and amyloid positron emission tomography (PET) with transitions from cognitively unimpaired (CU) to MCI in the Mayo Clinic Study of Aging (MCSA) and BioFINDER-2 studies. METHODS: Associations of continuous baseline plasma biomarker levels and amyloid PET Centiloid with progression to MCI, adjusting for age, sex, and education, were evaluated with Cox proportional hazards models. RESULTS: The study included 381 MCSA and 584 BioFINDER-2 participants. Amyloid PET and percent phosphorylated to non-phosphorylated tau217 (%p-tau217) were strong predictors of progression to MCI in both cohorts: hazard ratios of 1.49 and 1.23 in the MCSA and 1.72 and 1.65 in BioFINDER, respectively. Amyloid beta 42/40 was a significant predictor in BioFINDER-2 only (hazard ratio 2.20). DISCUSSION: Plasma %p-tau217 was associated with progression from CU to MCI in both cohorts, although differences in biomarker associations may be related to differences in the two cohorts. Highlights: Mass-spectrometry-based plasma phosphorylated tau217 was associated with cognitively unimpaired to mild cognitive impairment (MCI) progression. Plasma amyloid beta 42/40 was a significant predictor in BioFINDER but not the Mayo Clinic Study of Aging (MCSA). Amyloid positron emission tomography (PET) was the strongest predictor of progression to MCI in the MCSA. Plasma had added value to amyloid PET in BioFINDER but not the MCSA. Biomarker performance may vary with cohort and biomarker measurement differences.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, amyloid beta 42/40, amyloid beta positron emission tomography, mild cognitive impairment, phosphorylated tau 217, plasma biomarkers
in
Alzheimer's and Dementia
volume
21
issue
9
article number
e70625
publisher
Wiley
external identifiers
  • scopus:105014603381
  • pmid:40883967
ISSN
1552-5260
DOI
10.1002/alz.70625
language
English
LU publication?
yes
id
8992876e-344f-4a75-a4d1-527cdbc61209
date added to LUP
2025-10-16 13:25:41
date last changed
2026-01-09 10:59:01
@article{8992876e-344f-4a75-a4d1-527cdbc61209,
  abstract     = {{<p>INTRODUCTION: Plasma biomarkers’ utility for predicting incident mild cognitive impairment (MCI) remains unclear. We evaluated associations of plasma Alzheimer's disease (AD) biomarkers and amyloid positron emission tomography (PET) with transitions from cognitively unimpaired (CU) to MCI in the Mayo Clinic Study of Aging (MCSA) and BioFINDER-2 studies. METHODS: Associations of continuous baseline plasma biomarker levels and amyloid PET Centiloid with progression to MCI, adjusting for age, sex, and education, were evaluated with Cox proportional hazards models. RESULTS: The study included 381 MCSA and 584 BioFINDER-2 participants. Amyloid PET and percent phosphorylated to non-phosphorylated tau217 (%p-tau217) were strong predictors of progression to MCI in both cohorts: hazard ratios of 1.49 and 1.23 in the MCSA and 1.72 and 1.65 in BioFINDER, respectively. Amyloid beta 42/40 was a significant predictor in BioFINDER-2 only (hazard ratio 2.20). DISCUSSION: Plasma %p-tau217 was associated with progression from CU to MCI in both cohorts, although differences in biomarker associations may be related to differences in the two cohorts. Highlights: Mass-spectrometry-based plasma phosphorylated tau217 was associated with cognitively unimpaired to mild cognitive impairment (MCI) progression. Plasma amyloid beta 42/40 was a significant predictor in BioFINDER but not the Mayo Clinic Study of Aging (MCSA). Amyloid positron emission tomography (PET) was the strongest predictor of progression to MCI in the MCSA. Plasma had added value to amyloid PET in BioFINDER but not the MCSA. Biomarker performance may vary with cohort and biomarker measurement differences.</p>}},
  author       = {{Cogswell, Petrice M. and Wiste, Heather J. and Therneau, Terry M. and Griswold, Michael E. and Mattsson-Carlgren, Niklas and Palmqvist, Sebastian and Binette, Alexa Pichet and Stomrud, Erik and Bateman, Randall J. and Barthelemy, Nicolas and Braunstein, Joel B. and West, Tim and Verghese, Philip B. and Machulda, Mary M. and Graff-Radford, Jonathan and Algeciras-Schimnich, Alicia and Lowe, Val J. and Schwarz, Christopher G. and Senjem, Matthew L. and Gunter, Jeffrey L. and Knopman, David S. and Vemuri, Prashanthi and Petersen, Ronald C. and Hansson, Oskar and Jack, Clifford R.}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; amyloid beta 42/40; amyloid beta positron emission tomography; mild cognitive impairment; phosphorylated tau 217; plasma biomarkers}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Association of plasma Alzheimer's disease biomarkers with cognitive decline in cognitively unimpaired individuals}},
  url          = {{http://dx.doi.org/10.1002/alz.70625}},
  doi          = {{10.1002/alz.70625}},
  volume       = {{21}},
  year         = {{2025}},
}