Evidence map›Paper›PMID 41579901›Full record

Trial reportThe Lancet. Neurology2026

Safety and efficacy of crenezumab in cognitively unimpaired carriers of the PSEN1

Pierre N Tariot, Francisco S Lopera, Silvia Ríos-Romenets, Kaycee M Sink, Margarita Giraldo-Chica, Natalia Acosta-Baena, Gustavo Villegas, Alejandro Espinosa, Marisol Londoño Castaño, Claudia Muñoz and 34 more

Abstract readRandomized Controlled TrialClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Beyond the Cochrane review: Re-evaluating anti-amyloid therapy in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

44 authors.

Pierre N TariotBanner Alzheimer's Institute, Phoenix, AZ, USA. Electronic address: pierre.tariot@bannerhealth.com.
Francisco S LoperaNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Silvia Ríos-RomenetsNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Kaycee M SinkGenentech, San Francisco, CA, USA.
Margarita Giraldo-ChicaNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Natalia Acosta-BaenaNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Gustavo VillegasUniversity of Antioquia, Medellín, Colombia.
Alejandro EspinosaNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia; Hospital San Juan de Dios de Yarumal, Antioquia, Colombia.
Marisol Londoño CastañoNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Claudia MuñozNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Paula OspinaNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Yamile BocanegraNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Victoria TiradoNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Eliana HenaoNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Eugenia CardonaNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Ernesto LunaNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Hugo LopezNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Gregorio SánchezCardiomet Cequin, Universidad del Quindío, Armenia, Colombia; San Juan de Dios Hospital, Armenia, Colombia.
Mario Muñoz CollazosMarly's Clinic, Bogotá, Colombia.
Sergio AlvarezHospital Pablo Tobón Uribe, Medellín, Colombia.
David AguillónNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia.
Nan HuGenentech, San Francisco, CA, USA.
David ClaytonGenentech, San Francisco, CA, USA.
Tobias BittnerGenentech, San Francisco, CA, USA; F Hoffmann-La Roche, Basel, Switzerland.
Andres SchneiderF Hoffmann-La Roche, Basel, Switzerland.
Michael DoltonGenentech, San Francisco, CA, USA.
Victor PoonGenentech, San Francisco, CA, USA.
Jonas NguyenGenentech, San Francisco, CA, USA.
Ronald G ThomasHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, San Diego, CA, USA.
Lon S SchneiderKeck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Kewei ChenBanner Alzheimer's Institute, Phoenix, AZ, USA.
Yi SuBanner Alzheimer's Institute, Phoenix, AZ, USA.
Robert C AlexanderBanner Alzheimer's Institute, Phoenix, AZ, USA.
Yakeel T QuirozNeuroscience Group of Antioquia (GNA), University of Antioquia, Medellín, Colombia; Departments of Psychiatry and Neurology, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, USA.
Yuqi CaiDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Yi Ran XuDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Beth OstaszewskiDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Dennis J SelkoeDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nicholas J AshtonBanner Alzheimer's Institute, Phoenix, AZ, USA; Banner Sun Health Research Institute, Sun City, AZ, USA; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Marisa N DenkingerBanner Sun Health Research Institute, Sun City, AZ, USA.
Laura J JakimovichBanner Alzheimer's Institute, Phoenix, AZ, USA.
Rachelle S DoodyGenentech, San Francisco, CA, USA; F Hoffmann-La Roche, Basel, Switzerland.
Jessica B LangbaumBanner Alzheimer's Institute, Phoenix, AZ, USA.
Eric M ReimanBanner Alzheimer's Institute, Phoenix, AZ, USA.

Funding

Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI Nicholas Ashton · 2021 to 2026
$24.9M
Alzheimer's Prevention InitiativeRF1AG041705 · NIA · BANNER ALZHEIMER'S INSTITUTE · PI LOPERA, FRANCISCO, REIMAN, ERIC MICHAEL · 2012 to 2012
$15.3M
Alzheimer's Prevention Initiative ADAD Colombia TrialR01AG055444 · NIA · BANNER HEALTH · PI LOPERA, FRANCISCO, REIMAN, ERIC MICHAEL · 2017 to 2022
$14.9M
NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG072980NIA NIH HHS R01 AG055444NIA NIH HHS RF1 AG041705
6 · The paper itself

Abstract

backgroundTo have maximal benefit, Alzheimer's disease-modifying treatments might need to be started before the onset of clinical symptoms. Mutations of the PSEN1 gene are inherited as fully penetrant, autosomal-dominant traits, which almost always result in the clinical onset of Alzheimer's disease before the age of 65 years. We aimed to evaluate the efficacy, including possible delayed emergence of cognitive impairment, and safety of crenezumab, an anti-amyloid monoclonal antibody, in cognitively unimpaired carriers of the PSEN1

methodsThis 5-8-year common-close, double-blind, placebo-controlled, single-centre trial screened kindred members aged 30-60 years from the main health-care site in Medellín, Colombia. Participants who were cognitively unimpaired and carried the PSEN1

findings619 Colombian API registrants were prescreened, 315 were assessed for eligibility, and 252 were enrolled (crenezumab-carrier, n=85; placebo-carrier, n=84; placebo-non-carrier, n=83; 160 [63%] women and 92 [37%] men) between Dec 20, 2013, and Feb 27, 2017. 237 (94%) completed the trial, with final data collection on March 22, 2022. The annualised rate of change in the API ADAD composite was -1·10 (SE 0·29) in the crenezumab group and -1·43 (0·29) in the placebo group (between-group difference 0·33 [95% CI -0·48 to 1·13]; p=0·43). The annualised rate of change in FCSRT-CI was -0·03 (0·00) in the crenezumab group and -0·04 (0·00) in the placebo group (between-group difference 0·01 [0·00 to 0·02]; p=0·16). All participants had at least one adverse event; serious adverse events occurred in 23 (27%) of 84 in the crenezumab group and 21 (25%) of 84 in the placebo group. No fatalities occurred.

interpretationCrenezumab therapy administered for 5-8 years did not result in significant benefits on our primary clinical outcomes in cognitively unimpaired participants predisposed to developing ADAD dementia; secondary and exploratory outcomes also showed no significant effect on removal of amyloid plaques or other clinical or biomarker outcomes. Together with the results of other anti-amyloid β trials, robust fibrillar amyloid removal appears necessary for clinical efficacy in people with elevated brain amyloid. This study will further inform the biomarker, cognitive, and clinical trajectory of preclinical ADAD, the risk of clinical progression in amyloid-positive and amyloid-negative mutation carriers, and the size and design of future secondary and primary prevention trials.

fundingUS National Institute on Aging (NIA), Banner Alzheimer's Institute, Genentech, F Hoffmann-La Roche.

Indexed as

Alzheimer DiseaseAntibodies, Monoclonal, HumanizedPresenilin-1AdultColombiaDouble-Blind MethodFemaleHeterozygoteHumansMaleMiddle AgedMutationTreatment OutcomeAntibodies, Monoclonal, HumanizedcrenezumabPresenilin-1PSEN1 protein, human

Identifiers

PMID41579901
PMCPMC12994566

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.