Evidence map›Paper›PMID 35381062›Full record

ArticleBrain : a journal of neurology2022

Genetic evaluation of dementia with Lewy bodies implicates distinct disease subgroups.

Karri Kaivola, Zalak Shah, Ruth Chia, International LBD Genomics Consortium, Sonja W Scholz

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 2 pooled it
3.6field-weighted citation impact, top 5% 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

42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. TMEM106B is a selective modulator of TDP-43 pathology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. Shared genetic architecture between DTI-ALPS traits and neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Where do PDD and DLB SYNdromes fit in neuronal alpha-SYNuclein biological frameworks?Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  13. Progression ofFrontiers in aging neuroscience · 2026
    Article
  14. Heterogeneity of dementia with lewy bodies: Insights from clinical presentations, neuropathology, and biomarkers.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Review
  15. Review
  16. Article
  17. Review
  18. APOE ε4 linked effects on clinical features and neuropathology in dementia with Lewy bodies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 4 institutions in 2 countries.

Karri KaivolaDepartment of Neurology and Translational Immunology Program, University Hospital and Helsinki University, Helsinki, Finland.
Zalak ShahNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Ruth ChiaLaboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
International LBD Genomics Consortium
Sonja W ScholzNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.ORCID 0000-0002-6623-0429
Johns Hopkins University · USNational Institute of Neurological Disorders and Stroke · USNational Institute on Aging · USUniversity of Helsinki · FI

Funding

Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Research Education Core FP30AG072977 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SANDRA WEINTRAUB · 2021 to 2026
$26.3M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI Nicholas Ashton · 2021 to 2026
$24.9M
Longitudinal Imaging Biomarkers of Prodromal DLBU01NS100620 · NINDS · MAYO CLINIC ROCHESTER · PI Bradley F Boeve, KEJAL KANTARCI · 2017 to 2026
$19.2M
Genetic characterization of atypical parkinsonismZIANS003154 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI SCHOLZ, SONJA · 2016 to 2025
$15.4M
Genome sequencing of Lewy Body Dementia and Frontotemporal Dementia: a public resource for the study of Alzheimers disease and related dementiasZIAAG000935 · NIA · NATIONAL INSTITUTE ON AGING · PI TRAYNOR, BRYAN · 2017 to 2025
$771k
Intramural NIH HHS ZIA AG000935Intramural NIH HHS ZIA NS003154Medical Research Council G0701075Medical Research Council G0901254NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072980NINDS NIH HHS U01 NS100620
6 · The paper itself

Abstract

The APOE locus is strongly associated with risk for developing Alzheimer's disease and dementia with Lewy bodies. In particular, the role of the APOE ε4 allele as a putative driver of α-synuclein pathology is a topic of intense debate. Here, we performed a comprehensive evaluation in 2466 dementia with Lewy bodies cases versus 2928 neurologically healthy, aged controls. Using an APOE-stratified genome-wide association study approach, we found that GBA is associated with risk for dementia with Lewy bodies in patients without APOE ε4 (P = 6.58 × 10-9, OR = 3.41, 95% CI = 2.25-5.17), but not with dementia with Lewy bodies with APOE ε4 (P = 0.034, OR = 1.87, 95%, 95% CI = 1.05-3.37). We then divided 495 neuropathologically examined dementia with Lewy bodies cases into three groups based on the extent of concomitant Alzheimer's disease co-pathology: pure dementia with Lewy bodies (n = 88), dementia with Lewy bodies with intermediate Alzheimer's disease co-pathology (n = 66) and dementia with Lewy bodies with high Alzheimer's disease co-pathology (n = 341). In each group, we tested the association of the APOE ε4 against the 2928 neurologically healthy controls. Our examination found that APOE ε4 was associated with dementia with Lewy bodies + Alzheimer's disease (P = 1.29 × 10-32, OR = 4.25, 95% CI = 3.35-5.39) and dementia with Lewy bodies + intermediate Alzheimer's disease (P = 0.0011, OR = 2.31, 95% CI = 1.40-3.83), but not with pure dementia with Lewy bodies (P = 0.31, OR = 0.75, 95% CI = 0.43-1.30). In conclusion, although deep clinical data were not available for these samples, our findings do not support the notion that APOE ε4 is an independent driver of α-synuclein pathology in pure dementia with Lewy bodies, but rather implicate GBA as the main risk gene for the pure dementia with Lewy bodies subgroup.

Indexed as

Alzheimer DiseaseLewy Body DiseaseAgedalpha-SynucleinApolipoprotein E4Genome-Wide Association StudyHumansalpha-SynucleinApolipoprotein E4Alzheimer’s diseaseAPOEco-pathologydementia with Lewy bodies

Identifiers

PMID35381062
PMCPMC9423712
OpenAlexW4205374216

What OpenQuestion holds

Textmetadata
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.