Evidence map›Paper›PMID 40409316›Full record

ReviewThe Lancet. Neurology2025

Protective genetic variants against Alzheimer's disease.

Claudia Marino, Vincent Malotaux, Averi Giudicessi, David Aguillon, Diego Sepulveda-Falla, Francisco Lopera, Yakeel T Quiroz

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The Lancet. Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Programmed cell death: a promising management for Alzheimer's disease.Apoptosis : an international journal on programmed cell death · 2026
    Review
  4. Article
  5. Article
  6. Review
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

7 authors.

Claudia MarinoThe Schepens Eye Research Institute of Mass Eye and Ear and the Department of Ophthalmology at Harvard Medical School, Boston, MA, USA; Department of Neurology, Sealy Institute for Drug Discovery and Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX, USA.
Vincent MalotauxDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Averi GiudicessiDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Boston University, Department of Psychological and Brain Sciences, Boston, MA, USA.
David AguillonThe Neuroscience Group of Antioquia, School of Medicine, University of Antioquia, Medellín, Colombia.
Diego Sepulveda-FallaThe Institute of Neuropathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Francisco LoperaThe Neuroscience Group of Antioquia, School of Medicine, University of Antioquia, Medellín, Colombia.
Yakeel T QuirozDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Boston University, Department of Psychological and Brain Sciences, Boston, MA, USA; The Neuroscience Group of Antioquia, School of Medicine, University of Antioquia, Medellín, Colombia; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: yquiroz@mgh.harvard.edu.

Funding

Resilience to Cognitive Decline and Resistance to Alzheimer's Disease and Related Neurodegenerative Diseases in Individuals from Colombia with Autosomal Dominant DementiasRM1NS132996 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI AGUILLON, DAVID FERNANDO, ARBOLEDA-VELASQUEZ, JOSEPH · 2023 to 2023
$3.8M
Relationship between tau pathology and cognitive impairment in autosomal dominant Alzheimer's diseaseR01AG054671 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI QUIROZ, YAKEEL T. · 2017 to 2021
$3.8M
Nerve growth factor (NGF) metabolic dysfunction as a marker of cognitive decline in autosomal dominant Alzheimer's diseaseRF1AG077627 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI AGUILLON, DAVID FERNANDO, CUELLO, A CLAUDIO · 2022 to 2022
$2.0M
Examining Sex-Specific Effects on White Matter Integrity and Brain Function in Familial Alzheimer's Disease and Vascular DementiaF31NS134277 · NINDS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI Averi Jordin Giudicessi · 2024 to 2026
$129k
NIA NIH HHS R01 AG054671NIA NIH HHS RF1 AG077627NINDS NIH HHS F31 NS134277NINDS NIH HHS RM1 NS132996
6 · The paper itself

Abstract

Genetic studies can offer powerful insights for the development of disease-modifying therapies for Alzheimer's disease. Protective genetic variants that delay the onset of cognitive impairment have been found in people with sporadic Alzheimer's disease and in carriers of mutations that usually cause autosomal-dominant Alzheimer's disease in mid-life. The study of families who carry autosomal dominant mutations provides a unique opportunity to uncover genetic modifiers of disease progression, including rare variants in genes such as APOE and RELN. Understanding how these variants confer protection can help identify the biological pathways that contribute to cognitive resilience, such as the heparan-sulphate proteoglycan-APOE receptor pathway, the TREM-2-driven signalling pathways in the microglia, and phagocytosis. Therapies able to replicate the beneficial effects of these natural defences could provide novel strategies for slowing or preventing the progression of Alzheimer's disease.

Indexed as

Alzheimer DiseaseGenetic Predisposition to DiseaseGenetic VariationApolipoproteins EHumansMembrane GlycoproteinsReceptors, ImmunologicApolipoproteins EMembrane GlycoproteinsReceptors, ImmunologicTREM2 protein, human

Identifiers

PMID40409316
PMCPMC12614636

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.