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Abushakra S, Porsteinsson AP, Sabbagh M, et al. APOE ε4/ε4 homozygotes with early Alzheimer's disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline. Alzheimers Dement (N Y). 2020;6(1):e12117doi: 10.1002/trc2.12117.
Abushakra, S., Porsteinsson, A. P., Sabbagh, M., Bracoud, L., Schaerer, J., Power, A., Hey, J. A., Scott, D., Suhy, J., Tolar, M. (2020). APOE ε4/ε4 homozygotes with early Alzheimer's disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline. Alzheimer's & dementia (New York, N. Y.), 6(1), e12117. https://doi.org/10.1002/trc2.12117
Abushakra, Susan, et al. "APOE ε4/ε4 homozygotes with early Alzheimer's disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline." Alzheimer's & dementia (New York, N. Y.) vol. 6,1 (2020): e12117. doi: https://doi.org/10.1002/trc2.12117
Abushakra S, Porsteinsson AP, Sabbagh M, Bracoud L, Schaerer J, Power A, Hey JA, Scott D, Suhy J, Tolar M. APOE ε4/ε4 homozygotes with early Alzheimer's disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline. Alzheimers Dement (N Y). 2020 Dec 04;6(1):e12117. doi: 10.1002/trc2.12117. eCollection 2020. PMID: 33304988; PMCID: PMC7716452.
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Alzheimers Dement (N Y). 2020 Dec 04;6(1):e12117. doi: 10.1002/trc2.12117. eCollection 2020.

APOE ε4/ε4 homozygotes with early Alzheimer's disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline.

Alzheimer's & dementia (New York, N. Y.)

Susan Abushakra, Anton P Porsteinsson, Marwan Sabbagh, Luc Bracoud, Joel Schaerer, Aidan Power, John A Hey, David Scott, Joyce Suhy, Martin Tolar,

Affiliations

  1. Alzheon Inc. Framingham Massachusetts USA.
  2. Alzheimer's Disease Care Research and Education Program University of Rochester Rochester New York USA.
  3. Cleveland Clinic Lou Ruvo Center for Brain Health & University of Nevada Las Vegas Nevada USA.
  4. Bioclinica Lyon France.
  5. Bioclinica Newark California USA.

PMID: 33304988 PMCID: PMC7716452 DOI: 10.1002/trc2.12117

Abstract

INTRODUCTION: Hippocampal volume (HV) and cortical thickness are commonly used imaging biomarkers in Alzheimer's disease (AD) trials, and may have utility as selection criteria for enrichment strategies. Atrophy rates of these measures, in the high-risk apolipoprotein E (APOE) ε4/ε4 homozygous AD subjects are unknown.

METHODS: Data from Alzheimer's Disease Neuroimaging Initiative (ADNI-1) and a tramiprosate trial were analyzed in APOE ε4/ε4 and APOE ε3/ε3 subjects with mild cognitive impairment (MCI) or mild AD. Magnetic resonance imaging (MRI) data were centrally processed using FreeSurfer; total HV and composite average cortical thickness were derived and adjusted for age, head size, and education. Volumetric changes from baseline were assessed using Boundary Shift Integral, and correlated with cognitive changes.

RESULTS: APOE ε4/ε4 MCI subjects showed significantly higher % HV atrophy and cortical thinning at 12 months (4.4%, 3.1%, n = 29) compared to APOE ε3/ε3 subjects (2.8%, 1.8%, n = 93) and similarly in mild AD (7.4%, 4.7% n = 21 vs 5.4%, 3.3% n = 29). Differences were all significant at 24 months. Over 24 months, HV atrophy and cortical thinning correlated significantly with Alzheimer's Disease Assessment Scale-Cognitive subscale worsening in APOE ε4/ε4 MCI subjects, but not in mild AD.

DISCUSSION: Correlation of volumetric measures to cognitive change in APOE ε4/ε4 subjects with early AD supports their role as efficacy biomarkers. If confirmed in a Phase 3 trial with ALZ-801 (pro-drug of tramiprosate) in APOE ε4/ε4 early AD subjects, it may allow their use as surrogate outcomes in future treatment or prevention trials in AD.

© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.

Keywords: ALZ‐801; Alzheimer's disease; amyloid beta; amyloid oligomers; apolipoprotein E ε4/ε4 homozygotes; biomarkers; cortical thickness; hippocampus atrophy; tramiprosate

Conflict of interest statement

Dr. Susan Abushakra serves as the chief medical officer of Alzheon, Inc. and holds stock and stock options of Alzheon, Inc. Dr. Martin Tolar serves as the founder, president, and chief executive offic

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