Evidence map›Paper›PMID 37188781›Full record

ArticleNature medicine2023

Resilience to autosomal dominant Alzheimer's disease in a Reelin-COLBOS heterozygous man.

Francisco Lopera, Claudia Marino, Anita S Chandrahas, Michael O'Hare, Nelson David Villalba-Moreno, David Aguillon, Ana Baena, Justin S Sanchez, Clara Vila-Castelar, Liliana Ramirez Gomez and 32 more

Open access · hybridAbstract readCase ReportsComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed, 1 pooled it
32.2field-weighted citation impact, top 1% of its field
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

130 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.

  1. Pooled it
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  11. A lifespan staging model of basal forebrain cholinergic vulnerability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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70 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

42 authors at 9 institutions in 3 countries.

Francisco Lopera *Neuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia.
Claudia Marino *Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2332-2163
Anita S Chandrahas *Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
Michael O'Hare *Schepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
Nelson David Villalba-Moreno *Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
David AguillonNeuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia.ORCID http://orcid.org/0000-0003-2283-536X
Ana BaenaNeuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia.
Justin S SanchezDepartment of Neurology at Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4421-3078
Clara Vila-CastelarDepartment of Psychiatry at Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8779-1487
Liliana Ramirez GomezDepartment of Neurology at Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
Natalia ChmielewskaSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
Gabriel M OliveiraSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
Jessica Lisa LittauInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Kristin HartmannInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Kyungeun ParkInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Susanne KrasemannInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID http://orcid.org/0000-0001-8795-818X
Markus GlatzelInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID http://orcid.org/0000-0002-7720-8817
Dorothee SchoemakerSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
Lucia Gonzalez-BuendiaSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
Santiago Delgado-TiradoSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
Said Arevalo-AlquichireSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3366-7384
Kahira L Saez-TorresSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
Dhanesh AmarnaniSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.
Leo A KimSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9106-6416
Randall C MazzarinoSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7954-3283
Harper GordonSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0005-9561-5706
Yamile BocanegraNeuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia.ORCID http://orcid.org/0000-0003-3064-2509
Andres VillegasNeuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia.
Xiaowu GaiCenter for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Moiz BootwallaCenter for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Jianling JiCenter for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-4941-3538
Lishuang ShenCenter for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
Kenneth S KosikNeuroscience Research Institute, Department of Molecular Cellular Developmental Biology, University of California, Santa Barbara, CA, USA.ORCID http://orcid.org/0000-0003-3224-5179
Yi SuThe Banner Alzheimer's Institute, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0002-1946-8063
Yinghua ChenThe Banner Alzheimer's Institute, Phoenix, AZ, USA.
Aaron SchultzDepartment of Neurology at Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
Reisa A SperlingDepartment of Neurology at Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1535-6133
Keith JohnsonDepartment of Neurology at Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Eric M ReimanThe Banner Alzheimer's Institute, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0002-0705-3696
Diego Sepulveda-FallaInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. d.sepulveda-falla@uke.uni-hamburg.de.ORCID http://orcid.org/0000-0003-0176-2042
Joseph F Arboleda-VelasquezSchepens Eye Research Institute of Mass Eye and Ear and Department of Ophthalmology at Harvard Medical School, Boston, MA, USA. joseph_arboleda@meei.harvard.edu.ORCID http://orcid.org/0000-0002-3192-9117
Yakeel T QuirozNeuroscience Group of Antioquia, Medicine School, University of Antioquia, Medellín, Colombia. yquiroz@mgh.harvard.edu.ORCID http://orcid.org/0000-0001-9714-8244
Massachusetts Eye and Ear Infirmary · USUniversität Hamburg · DEHarvard University · USUniversidad de Antioquia · COAlzheimer's Association · USBrigham and Women's Hospital · USChildren's Hospital of Los Angeles · USUniversity of Southern California · USUniversity of California, Santa Barbara · US

Funding

API A4 Alzheimer's Prevention TrialR01AG058468 · NIA · BANNER HEALTH · PI AISEN, PAUL S., ALEXANDER, ROBERT C · 2018 to 2025
$31.9M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI JESSICA BROOKE LANGBAUM · 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
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
Charting vascular contributions to white matter disease in familial Alzheimer's disease and CADASILRF1NS110048 · NINDS · SCHEPENS EYE RESEARCH INSTITUTE · PI ARBOLEDA-VELASQUEZ, JOSEPH, SEPULVEDA-FALLA, DIEGO · 2018 to 2019
$3.6M
Role of Runx1 in Pathologic Ocular AngiogenesisR01EY027739 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI KIM, LEO A · 2018 to 2022
$2.8M
Memory network dysfunction as an early marker of preclinical Alzheimer's DiseaseDP5OD019833 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI QUIROZ, YAKEEL T. · 2014 to 2018
$2.3M
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
Exploring the Role of Aging in Cerebral Ischemic Small Vessel Disease Using Notch3 Mutant MiceUH3NS100121 · NINDS · SCHEPENS EYE RESEARCH INSTITUTE · PI ARBOLEDA-VELASQUEZ, JOSEPH · 2018 to 2020
$739k
Examining the impact of sex and hormones on the progression of autosomal dominant Alzheimer's diseaseK99AG073452 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI VILA CASTELAR, CLARA · 2022 to 2023
$268k
NEI NIH HHS R01 EY027739NIA NIH HHS K99 AG073452NIA NIH HHS P30 AG072980NIA NIH HHS R01 AG054671NIA NIH HHS R01 AG058468NIA NIH HHS RF1 AG041705NIA NIH HHS RF1 AG077627NIH HHS DP5 OD019833NINDS NIH HHS RF1 NS110048NINDS NIH HHS RM1 NS132996NINDS NIH HHS UH3 NS100121
6 · The paper itself

Abstract

We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.

Indexed as

Alzheimer DiseaseAnimalsFemaleHeterozygoteHumansMaleMiceNerve Tissue ProteinsReelin ProteinSignal TransductionDab1 protein, mouseNerve Tissue ProteinsReelin ProteinRELN protein, human

Identifiers

PMID37188781
PMCPMC10202812
OpenAlexW4376608964

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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.