Baseline and placebo-related imaging, cerebrospinal fluid, plasma biomarker, and cognitive findings in unimpaired PSEN1 E280A mutation carriers and non-carriers in the Alzheimer's Prevention Initiative Autosomal Dominant Alzheimer's Disease Colombia Trial.
rct · Level II
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- Also identified by DOI 10.1016/j.ebiom.2026.106390.
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Abstract
The Alzheimer's Prevention Initiative Autosomal Dominant Alzheimer's Disease (ADAD) Colombia Trial evaluated the biological, cognitive, and clinical effects of crenezumab, an anti-oligomeric and monomeric amyloid-beta (Aβ) monoclonal antibody, in 30-60-year-old PSEN1 E280A mutation carriers without cognitive impairment from the world's largest ADAD kindred, finding no significant treatment effects on Alzheimer's disease progression. This article describes baseline biomarker, cognitive, and clinical measurements and placebo-related longitudinal changes in the randomised prevention trial's mutation carrier and non-carrier groups. Crenezumab and placebo-treated mutation carriers and placebo-treated non-carriers were assessed using amyloid and fluorodeoxyglucose positron emission tomography (PET), magnetic resonance imaging, plasma, and optional tau PET and cerebrospinal fluid (CSF) biomarker, cognitive, and clinical measurements over 5-8 years. 94% of the 252 kindred members (85 crenezumab-treated mutation carriers, 84 placebo-treated carriers, and 83 placebo-treated non-carriers) completed the trial. 55% of the carriers had baseline PET evidence of substantial Aβ plaques. 32.9% and 6.8% of amyloid PET-positive and PET-negative carriers, respectively, 36.5%, 13.2%, and 0% of pTau217-positive, pTau217-intermediate, and pTau217-negative carriers, respectively, and no non-carriers became cognitively impaired over the next 5 years. Carriers were distinguished from non-carriers by several baseline and longitudinal Aβ, tau, neurodegenerative, and inflammatory biomarker measures, but not by CSF oligomeric Aβ measurements. Despite the absence of significant treatment effects, these findings and the trial itself continue to inform the course of preclinical ADAD, advance Alzheimer's disease prevention research, and provide a shared resource of data and samples for the field (ClinicalTrials.gov ID: NCT01998841; trial completed). National Institute on Aging, Banner Alzheimer's Institute, Genentech, Inc., and F. Hoffmann-La Roche Ltd.