APOE ε4-associated heterogeneity of neuroimaging biomarkers across the Alzheimer's disease continuum

Jason Mares; Gautam Kumar; Anurag Sharma; Sheina Emrani; Laura Beth McIntire; Jia Guo; Vilas Menon; Tal Nuriel; Alzheimer's Disease Neuroimaging Initiative

doi:10.1002/alz.14392

APOE ε4-associated heterogeneity of neuroimaging biomarkers across the Alzheimer's disease continuum

Alzheimers Dement. 2024 Nov 22. doi: 10.1002/alz.14392. Online ahead of print.

Authors

Jason Mares^{1

2}, Gautam Kumar^{1

3

4}, Anurag Sharma^{1

3}, Sheina Emrani⁵, Laura Beth McIntire⁶, Jia Guo^{7

8}, Vilas Menon^{1

2}, Tal Nuriel^{1

3}; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
² Department of Neurology, Columbia University, New York, New York, USA.
³ Department of Pathology and Cell Biology, Columbia University, New York, New York, USA.
⁴ Department of Neurobiology, University of Maryland, Baltimore, Maryland, USA.
⁵ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁶ Lipidomics and Biomarker Discovery Lab, Brain Health Imaging Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
⁷ Department of Psychiatry, Columbia University, New York, New York, USA.
⁸ Zuckerman Institute, Columbia University, New York, New York, USA.

PMID: 39575672
DOI: 10.1002/alz.14392

Abstract

Introduction: While the role of apolipoprotein E (APOE) ε4 in Alzheimer's disease (AD) susceptibility has been studied extensively, much less is known about the differences in disease presentation in APOE ε4 carriers versus non-carriers.

Methods: To help elucidate these differences, we performed a broad analysis comparing the regional levels of six different neuroimaging biomarkers in the brains of APOE ε4 carriers versus non-carriers who participated in the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Results: We observed significant APOE ε4-associated heterogeneity in regional amyloid beta deposition, tau accumulation, glucose uptake, brain volume, cerebral blood flow, and white matter hyperintensities within each AD diagnostic group. We also observed important APOE ε4-associated differences in cognitively unimpaired individuals who converted to mild cognitive impairment/AD versus those who did not convert.

Discussion: This observed heterogeneity in neuroimaging biomarkers between APOE ε4 carriers versus non-carriers may have important implications regarding the prevention, diagnosis, and treatment of AD in different subpopulations.

Highlights: An extensive study was performed on the apolipoprotein E (APOE) ε4-associated heterogeneity in neuroimaging biomarkers from the Alzheimer's Disease Neuroimaging Initiative. Robust APOE ε4-associated increases in amyloid beta (Aβ) deposition throughout the brain, in every diagnostic group, were observed. APOE ε4-associated increases in tau pathology, decreases in glucose uptake, and increases in brain atrophy, which expand in regional scope and magnitude with disease progression, were observed. Significant sex- and age-related differences in APOE ε4-associated neuroimaging biomarker heterogeneity, with overall increases in pathological presentation in female APOE ε4 carriers, were observed. Regional differences in Aβ deposition, tau accumulation, glucose uptake, ventricle size, and white matter hyperintensities were observed in cognitively normal participants who converted to mild cognitive impairment/Alzheimer's disease, which may hold potential predictive value.

Keywords: Alzheimer's Disease Neuroimaging Initiative; Alzheimer's disease; apolipoprotein E; biomarkers; heterogeneity; neuroimaging.

Abstract

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