Cerebral blood flow as a biomarker of resilience in cognitively unimpaired APOE ɛ4 carriers.
8 affiliations
- 1Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
- 2Department of Psychological Science, University of California, Irvine, California, USA.
- 3Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
- 4Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, California, USA.
- 5Department of Pathology and Laboratory Medicine, University of California, Irvine, Medical Sciences D, Irvine, California, USA.
- 6Department of Neurology, University of California, Irvine, Irvine, California, USA.
- 7Center for Innovations in Brain Science, Department of Pharmacology, University of Arizona, Tucson, Arizona, USA.
- 8Department of Psychology, University of Southern California, Dornsife College of Arts and Letters, Los Angeles, California, USA.
Abstract
Introduction
It remains unclear whether medial temporal lobe (MTL) hyperperfusion in cognitively unimpaired apolipoprotein E (APOE) ɛ4 carriers reflects resilience or dysfunction. We examined whether cortical MTL cerebral blood flow (CBF) relates to cognition differently in APOE ɛ4 carriers and noncarriers with and without AD pathophysiological changes.Methods
One hundred forty-eight cognitively unimpaired older adults underwent pseudo-continuous arterial spin labeling MRI to quantify MTL CBF and assessment of memory and executive function. In a subset (n = 126), AD pathology was indexed using plasma phosphorylated tau 217 (pTau₂₁₇).Results
APOE ɛ4 carriers showed higher MTL CBF than noncarriers. Higher MTL CBF was associated with better executive function only in pTau₂₁₇-negative APOE ɛ4 carriers. Interactions remained significant after adjusting for MTL cortical volume or white matter hyperintensities.Discussion
Hyperperfusion in cognitively unimpaired APOE ɛ4 carriers may reflect a resilience biomarker related to better cognitive function in the absence of detectable AD pathophysiological changes.Highlights
Apolipoprotein E (APOE) ɛ4 carriers show elevated medial temporal lobe (MTL) cerebral blood flow (CBF). Higher MTL CBF is linked to better executive function in APOE ɛ4 carriers. This association is only observed in APOE ɛ4 carriers who are pTau₂₁₇-negative. MTL hyperperfusion may mark resilience in APOE ɛ4 carriers at risk for AD.
Related
- CSF and plasma lipid profiling predicts risk of cognitive impairment in cognitively unimpaired older adults
- White matter hyperintensities and amyloid pathology in cognitively unimpaired aging: topographical, microstructural, and network-level evidence
- Age-dependent gray matter correlates of perceived financial exploitation vulnerability in cognitively unimpaired older adults.
- Associations Between Biomarkers of Alzheimer's Disease and Sleep in Cognitively Unimpaired Older Adults.
- Longitudinal associations of hormone therapy and depressive symptoms in cognitively unimpaired older women
BibTeX
@article{quiring2026cerebral,
title = {{Cerebral blood flow as a biomarker of resilience in cognitively unimpaired APOE ɛ4 carriers.}},
author = {Melanie Quiring and Arunima Kapoor and John Paul M Alitin and Basant Lashin and Jillian L Joyce and Allison C Engstrom and Trevor Lohman and Aimée Gaubert and Fatemah Shenasa and Kevin W Law and Farrah Ferrer and Danny J J Wang and Elizabeth Head and Rond Malhas and Kathleen Rodgers and S Duke Han and Daniel A Nation},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2026},
month = oct,
doi = {10.1002/alz.71934},
url = {https://europepmc.org/article/MED/42908099},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Cerebral blood flow as a biomarker of resilience in cognitively unimpaired APOE ɛ4 carriers.
AU - Melanie Quiring
AU - Arunima Kapoor
AU - John Paul M Alitin
AU - Basant Lashin
AU - Jillian L Joyce
AU - Allison C Engstrom
AU - Trevor Lohman
AU - Aimée Gaubert
AU - Fatemah Shenasa
AU - Kevin W Law
AU - Farrah Ferrer
AU - Danny J J Wang
AU - Elizabeth Head
AU - Rond Malhas
AU - Kathleen Rodgers
AU - S Duke Han
AU - Daniel A Nation
PY - 2026
DA - 2026/10/01
JO - Alzheimer's & dementia : the journal of the Alzheimer's Association
DO - 10.1002/alz.71934
UR - https://europepmc.org/article/MED/42908099
AB - Introduction It remains unclear whether medial temporal lobe (MTL) hyperperfusion in cognitively unimpaired apolipoprotein E (APOE) ɛ4 carriers reflects resilience or dysfunction. We examined whether cortical MTL cerebral blood flow (CBF) relates to cognition differently in APOE ɛ4 carriers and noncarriers with and without AD pathophysiological changes.Methods One hundred forty-eight cognitively unimpaired older adults underwent pseudo-continuous arterial spin labeling MRI to quantify MTL CBF and assessment of memory and executive function. In a subset (n = 126), AD pathology was indexed using plasma phosphorylated tau 217 (pTau₂₁₇).Results APOE ɛ4 carriers showed higher MTL CBF than noncarriers. Higher MTL CBF was associated with better executive function only in pTau₂₁₇-negative APOE ɛ4 carriers. Interactions remained significant after adjusting for MTL cortical volume or white matter hyperintensities.Discussion Hyperperfusion in cognitively unimpaired APOE ɛ4 carriers may reflect a resilience biomarker related to better cognitive function in the absence of detectable AD pathophysiological changes.Highlights Apolipoprotein E (APOE) ɛ4 carriers show elevated medial temporal lobe (MTL) cerebral blood flow (CBF). Higher MTL CBF is linked to better executive function in APOE ɛ4 carriers. This association is only observed in APOE ɛ4 carriers who are pTau₂₁₇-negative. MTL hyperperfusion may mark resilience in APOE ɛ4 carriers at risk for AD.
SN - 1552-5260
SN - 1552-5279
ER -