Evidence map›Paper›PMID 35393555›Full record

ReviewMolecular psychiatry2022

Dissecting the clinical heterogeneity of early-onset Alzheimer's disease.

Daniel W Sirkis, Luke W Bonham, Taylor P Johnson, Renaud La Joie, Jennifer S Yokoyama

Open access · hybridAbstract readReview
In one paragraph

Review in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 3 pooled it
14.0field-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

81 citing papers in PubMed, 3 syntheses or guidelines pooled it, 124 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Observational
  7. Article
  8. Article
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  10. Article
  11. Article
  12. Article
  13. Article
  14. Distinct Tau PET Dynamics in Early vs. Late Age-of-Onset Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026
    Article
  15. Alzheimer's disease polygenic risk in early- and late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

21 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Daniel W SirkisMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, 94158, USA.
Luke W BonhamMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, 94158, USA.
Taylor P JohnsonMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, 94158, USA.
Renaud La JoieMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0003-2581-8100
Jennifer S YokoyamaMemory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, 94158, USA. jennifer.yokoyama@ucsf.edu.ORCID http://orcid.org/0000-0001-7274-2634
University of California, San Francisco · US

Funding

Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Gil Dan Rabinovici · 2019 to 2026
$36.9M
Tau Metabolism in FTD: From Gene Mutations to Molecular Chaperones and Lysosomal ProteasesU54NS123985 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KARCH, CELESTE MARIE · 2021 to 2025
$9.0M
US-South American Initiative for Genetic-Neural-Behavioral Interactions in Human Neurodegenerative ResearchR01AG057234 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Claudia Duran-Aniotz, Agustin M. Ibanez · 2019 to 2026
$6.1M
Elucidating clinical heterogeneity in early-onset AD via genomics, transcriptomics, and neuroimagingR01AG062588 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOKOYAMA, JENNIFER S · 2019 to 2023
$4.0M
Circadian Disturbance and Dementia in Latin AmericaR01AG083799 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Kun Hu, Agustin M. Ibanez · 2023 to 2026
$3.0M
Connectome-based spread of neurodegenerative processes in Alzheimer's diseaseK99AG065501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LA JOIE, RENAUD CHARLES · 2020 to 2021
$253k
NIA NIH HHS K99 AG065501NIA NIH HHS P30 AG062422NIA NIH HHS R01 AG057234NIA NIH HHS R01 AG062588NIA NIH HHS R01 AG083799NINDS NIH HHS U54 NS123985
6 · The paper itself

Abstract

Early-onset Alzheimer's disease (EOAD) is a rare but particularly devastating form of AD. Though notable for its high degree of clinical heterogeneity, EOAD is defined by the same neuropathological hallmarks underlying the more common, late-onset form of AD. In this review, we describe the various clinical syndromes associated with EOAD, including the typical amnestic phenotype as well as atypical variants affecting visuospatial, language, executive, behavioral, and motor functions. We go on to highlight advances in fluid biomarker research and describe how molecular, structural, and functional neuroimaging can be used not only to improve EOAD diagnostic acumen but also enhance our understanding of fundamental pathobiological changes occurring years (and even decades) before the onset of symptoms. In addition, we discuss genetic variation underlying EOAD, including pathogenic variants responsible for the well-known mendelian forms of EOAD as well as variants that may increase risk for the much more common forms of EOAD that are either considered to be sporadic or lack a clear autosomal-dominant inheritance pattern. Intriguingly, specific pathogenic variants in PRNP and MAPT-genes which are more commonly associated with other neurodegenerative diseases-may provide unexpectedly important insights into the formation of AD tau pathology. Genetic analysis of the atypical clinical syndromes associated with EOAD will continue to be challenging given their rarity, but integration of fluid biomarker data, multimodal imaging, and various 'omics techniques and their application to the study of large, multicenter cohorts will enable future discoveries of fundamental mechanisms underlying the development of EOAD and its varied clinical presentations.

Indexed as

Alzheimer DiseaseAge of OnsetHumansLanguageMulticenter Studies as TopicPhenotypeSyndrome

Identifiers

PMID35393555
PMCPMC9156414
OpenAlexW4225634431

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.