Alzheimer's & dementia (Amsterdam, Netherlands) · 2026
Anti-amyloid therapy eligibility in a longitudinal brain-donor cohort with post mortem confirmation.
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Haque Monjurul, Brookes Keeley J, Shao Beili
Аннотация
INTRODUCTION: Anti-amyloid therapies (AATs) for Alzheimer's disease (AD) demonstrate modest benefit in trials, but real-world eligibility remains uncertain. Requirements including biomarker confirmation and safety exclusions may limit access.
METHODS: Using the Brains for Dementia Research cohort, we linked longitudinal cognitive data with post mortem neuropathology to estimate trial-like AAT eligibility. Early stage was defined using harmonized cognitive thresholds. AD pathology required Thal amyloid phase ≥3 and Braak stage ≥IV. Exclusions were applied hierarchically: (1) vascular neuropathology, (2) anticoagulant use, and (3) apolipoprotein E (APOE) ε4/ε4 homozygosity.
RESULTS: Of 1230 participants, 945 had sufficient data; 232 had early, pathology-confirmed AD. Vascular pathology excluded 70.7%, anticoagulant use 19.1%, and APOE ε4/ε4 homozygosity 3.6% of remaining cases. Overall, 53 individuals (4.3% of those screened) were eligible. Eligibility declined with age and was driven primarily by vascular comorbidity.
DISCUSSION: Using a conservative pathology-anchored framework, only a small proportion of this older brain-donor cohort met trial-like eligibility criteria.
METHODS: Using the Brains for Dementia Research cohort, we linked longitudinal cognitive data with post mortem neuropathology to estimate trial-like AAT eligibility. Early stage was defined using harmonized cognitive thresholds. AD pathology required Thal amyloid phase ≥3 and Braak stage ≥IV. Exclusions were applied hierarchically: (1) vascular neuropathology, (2) anticoagulant use, and (3) apolipoprotein E (APOE) ε4/ε4 homozygosity.
RESULTS: Of 1230 participants, 945 had sufficient data; 232 had early, pathology-confirmed AD. Vascular pathology excluded 70.7%, anticoagulant use 19.1%, and APOE ε4/ε4 homozygosity 3.6% of remaining cases. Overall, 53 individuals (4.3% of those screened) were eligible. Eligibility declined with age and was driven primarily by vascular comorbidity.
DISCUSSION: Using a conservative pathology-anchored framework, only a small proportion of this older brain-donor cohort met trial-like eligibility criteria.