Baseline and placebo-related imaging, cerebrospinal fluid, plasma biomarker, and cognitive findings in…

Cohort studyEBioMedicine· Jul 2026

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.

Tobias Bittner, Francisco Lopera, Silvia Rios-Romenets … Eric M Reiman

Neurologic ImagingCohort studyPrognosisQ1IF 10.2

Over half of unimpaired PSEN1 E280A carriers already show amyloid plaques on positron emission tomography

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.

Tobias Bittner … Eric M Reiman

EBioMedicine · Jul 2026 · Q1 in General Medicine

Background

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.

Purpose

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.

Methods

Crenezumab and placebo-treated mutation carriers and placebo-treated non-carriers were assessed using amyloid and fluorodeoxyglucose positron emission tomography (positron emission tomography), magnetic resonance imaging, plasma, and optional tau positron emission tomography and cerebrospinal fluid (cerebrospinal fluid) biomarker, cognitive, and clinical measurements over 5-8 years.

n = 252 kindred members

55%

Results

55%

more than half already have amyloid buildup with no symptoms yet

n = 252 kindred members

More results

94% of the 252 kindred members (85 crenezumab-treated mutation carriers, 84 placebo-treated carriers, and 83 placebo-treated non-carriers) completed the trial.

More results

32.9% and 6.8% of amyloid positron emission tomography-positive and positron emission tomography-negative carriers, respectively, 36.5%, 13.2%, and 0% of Tau217-positive, Tau217-intermediate, and Tau217-negative carriers, respectively, and no non-carriers became cognitively impaired over the next 5 years.

“

Conclusion

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).

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.

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.

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