Evidence map›Paper›PMID 42534986›Full record

ArticleFrontiers in aging neuroscience2026

Mapping Alzheimer's disease heterogeneity through exploratory unsupervised learning.

Catarina Xavier, Ana Paula Correia, Joana Lopes, Joana Fernandes, Inês Laranjinha, Nádia Pinto

Abstract read
In one paragraph

Article in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Catarina Xavieri3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Ana Paula CorreiaULSSA - Unidade Local de Saúde de Santo António, Porto, Portugal.
Joana LopesULSSA - Unidade Local de Saúde de Santo António, Porto, Portugal.
Joana FernandesULSSA - Unidade Local de Saúde de Santo António, Porto, Portugal.
Inês LaranjinhaULSSA - Unidade Local de Saúde de Santo António, Porto, Portugal.
Nádia Pintoi3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.

Funding

Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MONICA G. RIVERA-MINDT · 2016 to 2026
$226.7M
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer-type DementiasRF1AG051550 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KLING, MITCHEL ALLAN · 2015 to 2016
$6.3M
Metabolic Networks and Pathways in Alzheimer's DiseaseR01AG046171 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F · 2014 to 2017
$4.4M
NIA NIH HHS R01 AG046171NIA NIH HHS RF1 AG051550NIA NIH HHS U01 AG024904NIA NIH HHS U19 AG024904
6 · The paper itself

Abstract

Introduction: Alzheimer's disease (AD) is becoming one of the most pressing health challenges of the century, affecting circa 55 million people worldwide and expected to triple this number by 2050. Besides the growing prevalence, AD remains difficult to diagnose due to its long preclinical phase and substantial symptomatic heterogeneity. Despite the existence of international guidelines for AD diagnosis emphasizing the use of biomarkers (such as neuroimaging and cerebrospinal molecular biomarkers), most research studies are still using data disregarding their diagnostic quality, blurring the overall statistical outcomes. Aiming to circumvent this effect, biomarker confirmed samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used, which integrate genetic and neuroimaging data for all participants. Methods: Unsupervised machine learning clustering methods were tested to explore whether curated genetic markers can reveal underlying substructure within sporadic AD (sAD). Here two specific sets of single nucleotide polymorphisms (SNPs) were selected: (i) candidate SNPs highlighted in previous studies that identified the existence of different subtypes in sAD and (ii) SNPs found associated with sAD in genome wide association studies (GWAS) that used at least 50% of samples with biomarker-confirmed diagnosis. Results: This strategy minimized background noise and enabled the construction of high quality SNP sets for analysis. Different clustering algorithms were evaluated with agglomerative hierarchical clustering consistently yielding the most robust performance. Across SNP sets, most trials revealed a reproducible binary structure within sAD samples, suggesting the presence of genetically distinguishable subgroups. Discussion: These findings align with emerging multimodal evidence supporting biological heterogeneity in AD. Overall, this work demonstrates that curated SNP panels combined with unsupervised learning can uncover meaningful substructure in sAD, reinforcing the value of integrating high quality genetic data into subtype research.

Indexed as

Alzheimer’s diseaseclustering algorithmsmachine learningsubtypingunsupervised learning

Identifiers

PMID42534986
PMCPMC13422478

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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.