Evidence map›Paper›PMID 38115150›Full record

ReviewActa neuropathologica communications2023

Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer's disease pathology: a population-based autopsy study in an admixed sample.

Regina Silva Paradela, Alberto Fernando Oliveira Justo, Vítor Ribeiro Paes, Renata E P Leite, Carlos A Pasqualucci, Lea T Grinberg, Michel Satya Naslavsky, Mayana Zatz, Ricardo Nitrini, Wilson Jacob-Filho and 1 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Acta neuropathologica communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–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

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  6. Clinical Management of Cerebral Amyloid Angiopathy.Journal of clinical medicine · 2025
    Review
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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

11 authors.

Regina Silva ParadelaDivision of Geriatrics, University of São Paulo Medical School, 455 Doutor Arnaldo Avenue, room 1355, São Paulo, SP, Brazil. reginaps@usp.br.ORCID 0000-0003-3155-4682
Alberto Fernando Oliveira JustoDivision of Geriatrics, University of São Paulo Medical School, 455 Doutor Arnaldo Avenue, room 1355, São Paulo, SP, Brazil.
Vítor Ribeiro PaesDepartment of Pathology, University of Sao Paulo Medical School, São Paulo, Brazil.
Renata E P LeiteDepartment of Pathology, University of Sao Paulo Medical School, São Paulo, Brazil.
Carlos A PasqualucciDepartment of Pathology, University of Sao Paulo Medical School, São Paulo, Brazil.
Lea T GrinbergMemory and Aging Center, University of California, San Francisco, USA.
Michel Satya NaslavskyHuman Genome and Stem Cell Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
Mayana ZatzHuman Genome and Stem Cell Center, Biosciences Institute, University of São Paulo, São Paulo, Brazil.
Ricardo NitriniDepartment of Neurology, University of São Paulo Medical School, São Paulo, Brazil.
Wilson Jacob-FilhoDivision of Geriatrics, University of São Paulo Medical School, 455 Doutor Arnaldo Avenue, room 1355, São Paulo, SP, Brazil.
Claudia Kimie SuemotoDivision of Geriatrics, University of São Paulo Medical School, 455 Doutor Arnaldo Avenue, room 1355, São Paulo, SP, Brazil.

Funding

Investigating regional and cellular vulnerabilities to tau pathology in young-onset Alzheimer's diseaseR01AG075802 · NIA · MAYO CLINIC JACKSONVILLE · PI BERNARDINO Francesco GHETTI, Lea Tenenholz Grinberg · 2022 to 2026
$15.5M
Clinical Features and Neuropathological Basis of Sleep Wake Behavior in Alzheimer's and PSPR01AG060477 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lea Tenenholz Grinberg, Thomas C Neylan · 2019 to 2026
$8.2M
Neuropathological changes underlying clinical heterogeneity in Alzheimer diseaseK24AG053435 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRINBERG, LEA TENENHOLZ · 2016 to 2025
$1.8M
Alzheimer's Association AARG-20-678884NIA NIH HHS K24 AG053435NIA NIH HHS R01 AG060477NIA NIH HHS R01 AG075802
6 · The paper itself

Abstract

backgroundApolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample.

methodsNeuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43).

resultsWe included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (β = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (β = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition.

conclusionThe association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.

Indexed as

Alzheimer DiseaseArteriosclerosisCerebral Amyloid AngiopathyLewy Body DiseaseStroke, LacunarAgedAged, 80 and overAllelesApolipoprotein E4Apolipoproteins EAutopsyCognitionDNA-Binding ProteinsFemaleGenotypeHumansApoE protein, humanApolipoprotein E4Apolipoproteins EDNA-Binding ProteinsApolipoprotein ECognitionDementiaMediation analysisNeuritic plaquesNeurofibrillary tangles

Identifiers

PMID38115150
PMCPMC10731799

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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.