ArticleAlzheimer's & dementia (New York, N. Y.)2020
APOE ε4/ε4 homozygotes with early Alzheimer's disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline.
Article in Alzheimer's & dementia (New York, N. Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
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- Sex differences in cognitive resilience in preclinical autosomal-dominant Alzheimer's disease carriers and non-carriers: Baseline findings from the API ADAD Colombia Trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Trial
- Lecanemab appropriate use recommendations for clinical practice in the UK.Journal of neurology, neurosurgery, and psychiatry · 2026Review
- Review
- The effect of Apolipoprotein E4 on cognitive function in Parkinson's disease: A structural MRI study in the PPMI cohort.PloS one · 2026Article
- The association of human apolipoprotein ε4 with dementia, cognition, imaging, and plasma biomarkers of neurodegeneration in a sample of older adults in the Democratic Republic of the Congo.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Information Geometry and Manifold Learning: A Novel Framework for Analyzing Alzheimer's Disease MRI Data.Diagnostics (Basel, Switzerland) · 2025Article
- Identifying network state-based Parkinson's disease subtypes using clustering and support vector machine models.Frontiers in psychiatry · 2025Article
- The role ofFrontiers in neuroscience · 2025Review
- AAVrh.10 delivery of novel APOE2-Christchurch variant suppresses amyloid and Tau pathology in Alzheimer's disease mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- APOE4-related differences in cortical thickness are modulated by sex in middle age.Brain imaging and behavior · 2024Article
- Article
- Traffic-related air pollution andFrontiers in dementia · 2024Article
- Domino-like effect of C112R mutation on ApoE4 aggregation and its reduction by Alzheimer's Disease drug candidate.Molecular neurodegeneration · 2023Article
- The prevalence of mild cognitive impairment in Gulf War veterans: a follow-up study.Frontiers in neuroscience · 2023Article
- Mediation of Reduced Hippocampal Volume by Cerebral Amyloid Angiopathy in Pathologically Confirmed Patients with Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Article
- Apolipoprotein E ε4 accelerates the longitudinal cerebral atrophy in open access series of imaging studies-3 elders without dementia at enrollment.Frontiers in aging neuroscience · 2023Article
- Impact of sex and APOE-Frontiers in neurology · 2023Article
- Obesity-Related Neuroinflammation: Magnetic Resonance and Microscopy Imaging of the Brain.International journal of molecular sciences · 2022Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionHippocampal 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.
methodsData 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.
resultsAPOE 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.
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