Evidence map›Paper›PMID 40219863›Full record

SynthesisAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis.

Yajing Zhou, Rory Sheehan, Lizhi Guo, Andre Strydom

Abstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

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

  1. Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Pooled it
  2. Article
  3. Article
  4. Alterations of gut microbiota in Down syndrome and their association with Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Biomarkers in preclinical and early Alzheimer's disease in China: a scoping review.The journal of prevention of Alzheimer's disease · 2026
    Article
  6. Article
  7. Age predicts Alzheimer's in Down syndrome better than MRI, plasma, or cognition.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  8. Article
  9. Precision medicine for Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  10. Article
  11. Article
  12. Article
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

4 authors.

Yajing ZhouDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Rory SheehanDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Lizhi GuoDepartment of Psychology, The Chinese University of Hong Kong, Hong Kong, China.
Andre StrydomDepartment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Funding

China Scholarship Council 202308440138King's-China Scholarship Council PhD Scholarship Programme
6 · The paper itself

Abstract

Individuals with Down syndrome (DS) are at high risk of Alzheimer's disease (AD), displaying AD pathology similar to the general population. This study evaluated AD-related blood biomarkers in DS within the AT(N) framework through a systematic review and meta-analysis of studies published between 2017 and October 2024. The meta-analysis focused on plasma amyloid beta (Aβ)42, Aβ40, total tau (t-tau), phosphorylated tau (p-tau)181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) levels, comparing 2109 DS individuals and 1006 euploid controls. Plasma Aβ42, Aβ40, NfL, and GFAP levels were significantly elevated in DS compared to euploid controls, while the Aβ42/40 ratio was reduced. In DS-AD individuals, Aβ42 and t-tau levels were elevated, with p-tau181, NfL, and GFAP consistently high across clinical subgroups. Notably, Aβ40 and the Aβ42/40 ratio changed significantly in preclinical AD, while t-tau increased in clinical AD. Incorporating inflammation (I) markers highlights neuroinflammation's role in DS-AD progression, supporting the blood-based AT(N)I framework for early AD detection and monitoring in DS. HIGHLIGHTS: We reviewed 58 studies on Down syndrome (DS) blood biomarkers and a meta-analysis of 18 using single molecule array. Plasma amyloid beta (Aβ)42, Aβ40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) levels were elevated in DS compared to controls. DS-Alzheimer's disease (AD) individuals showed higher Aβ42, total tau (t-tau), phosphorylated tau (p-tau)181, NfL, and GFAP levels. Plasma p-tau181, NfL, and GFAP were elevated across all clinical subgroups. Aβ40 and Aβ42/40 ratio changed in preclinical AD; t-tau rose in clinical AD.

Indexed as

Alzheimer DiseaseBiomarkersDown SyndromeAmyloid beta-PeptidesGlial Fibrillary Acidic ProteinHumansNeurofilament ProteinsPeptide Fragmentstau ProteinsAmyloid beta-PeptidesBiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsPeptide Fragmentstau ProteinsAlzheimer's diseaseamyloidbiomarkersbloodDown syndromeneurodegenerationneuroinflammationplasmatau

Identifiers

PMID40219863
PMCPMC11992652

What OpenQuestion holds

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Registered trials

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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.