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Gene expression

Are there molecular subtypes of Alzheimer brains?

Eteleeb AM, Novotny BC, Tarraga CS, et al. · PLoS biology · 2024

Open access · cc by · source: Europe PMC

Brain multi-omics integration found four multimodal AD profiles, including severe Knight-C4 with worse cognition and heavy molecular dysregulation.

Study at a glance

Design
Computational / modelling — Multi-cohort brain multi-omics ML clustering of AD molecular profiles
N
N=42 · Knight-C4 high-dysregulation cluster n=42 within four multimodal profiles
Population
Human AD brain cohorts with multi-omic + clinical/neuropath data
Outcome
Multimodal molecular clusters linked to cognition and progression

Structured fields used in claim comparison tables when every cited study has a complete layer.

Key findings

Four profiles emerged; one severe profile had poor cognition, faster progression, shorter survival, neurodegeneration/astrogliosis, and reduced metabolomic signals. Knight-C4 (n=42) showed pronounced multi-layer dysregulation.

Methodology

Integrated transcriptomic, proteomic, metabolomic, and lipidomic profiles with clinical/neuropathological data using machine learning and clustered multimodal profiles.

Limitations

Clusters are observational patterns, not proven treatment-response groups.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • Brain multi-omics reveals multimodal AD molecular profiles including a severe cluster.

    Integrating transcriptomic/proteomic/metabolomic/lipidomic brain data yielded four multimodal profiles, including Knight-C4 with pronounced dysregulation and worse clinical features.

    Evidence for the claim as stated.

  • Specialty clinics are delivering lecanemab with real-world workflow constraints.

    A specialty memory-clinic report on lecanemab treatment adds practice-level evidence beside biomarker/pathology marker papers.

    Scope note — molecular subtypes ≠ treatment eligibility/outcomes

    Limits the claim's scope: a different population, assay, or outcome.

History

When this study was placed

Dated entries from the concept change log — when this paper was added or removed as support, challenge, or qualifier on a claim.

  1. 2026-09-15

    Placed as supporting evidence on Alzheimer’s and MCI markers

    Integrating transcriptomic/proteomic/metabolomic/lipidomic brain data yielded four multimodal profiles, including Knight-C4 with pronounced dysregulation and worse clinical features.

  2. 2026-09-15

    Placed as a scope qualifier on Alzheimer’s and MCI markers

    A specialty memory-clinic report on lecanemab treatment adds practice-level evidence beside biomarker/pathology marker papers.

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