Evidence map›Paper›PMID 42103686›Full record

SynthesisNeuropathology and applied neurobiology2026

Asymptomatic Versus Symptomatic Alzheimer's Disease Neuropathology: A Systematic Review of Differences Reported in Post-Mortem Studies.

Thiago Guilherme Rêgo Barros, Laura Barbosa Grossi, Maria Letícia da Silva Campos, Israel Bem-Hur Netto Cardoso, Antônio Lúcio Teixeira, Aline Silva de Miranda, Eliana Cristina de Brito Toscano

Abstract readSystematic Review
In one paragraph

Synthesis in Neuropathology and applied neurobiology, 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
0cells of the map it votes in
0citing papers in PubMed
–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

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

7 authors.

Thiago Guilherme Rêgo BarrosLaboratório Integrado de Pesquisas em Patologia, Departamento de Patologia, Faculdade de Medicina, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil.ORCID 0009-0004-9941-2351
Laura Barbosa GrossiLaboratório Integrado de Pesquisas em Patologia, Departamento de Patologia, Faculdade de Medicina, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil.ORCID 0000-0001-9982-2378
Maria Letícia da Silva CamposLaboratório Integrado de Pesquisas em Patologia, Departamento de Patologia, Faculdade de Medicina, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil.ORCID 0009-0007-2282-8238
Israel Bem-Hur Netto CardosoLaboratório Integrado de Pesquisas em Patologia, Departamento de Patologia, Faculdade de Medicina, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil.ORCID 0009-0005-9657-3675
Antônio Lúcio TeixeiraThe Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, Lozano Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.ORCID 0000-0002-9621-5422
Aline Silva de MirandaLaboratório de Neurobiologia "Conceição Machado", Departamento de Morfologia, Instituto de Ciência Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.ORCID 0000-0003-2811-7924
Eliana Cristina de Brito ToscanoLaboratório Integrado de Pesquisas em Patologia, Departamento de Patologia, Faculdade de Medicina, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil.ORCID 0000-0002-8756-0689

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico 306078/2025-2Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de Minas Gerais APQ 0158424
6 · The paper itself

Abstract

A subset of individuals exhibit substantial Alzheimer's disease (AD) neuropathology but remain asymptomatic (ASYMAD). The biological processes underlying this phenomenon remain poorly understood. We searched the PubMed/MEDLINE, Web of Science and CAPES databases to synthesise post-mortem brain tissue findings that differ between symptomatic and asymptomatic AD. Thirty-four studies met the predefined eligibility criteria. Multiple reports described lower levels of oligomeric Aβ and p-tau in ASYMAD, with reduced accumulation at synapses. Consistent with synaptic resilience, ASYMAD showed preserved expression of markers and proteomic signatures linked to synaptic function, homeostasis and plasticity. Further analyses supported preserved parenchymal architecture and dendritic and axonal morphology in ASYMAD. Some authors also described compensatory adaptations, including neuronal hypertrophy, increased neurogenesis and cellular antioxidant responses in ASYMAD brains. Additional findings indicated partial resistance to disruption of brain glucose, polyunsaturated fatty acid and one-carbon/polyamine metabolism. Glial and immune findings suggested a profile characterised by increased glial reactivity in specific regions and disease stages, alongside preserved glial homeostasis and lower cytokine expression in other contexts. In conclusion, although this review identified multiple processes potentially associated with the ASYMAD phenotype, the current evidence remains largely descriptive. Additionally, this synthesis is limited by substantial methodological heterogeneity and inconsistencies in data reporting. Future research should prioritise standardised clinicopathological definitions, pathology stage matching between ASYMAD and symptomatic AD groups, systematic assessment of mixed pathologies and further replication of exploratory findings to better elucidate the mechanisms underlying clinical resilience to AD neuropathology.

Indexed as

Alzheimer DiseaseBrainAutopsyHumansAlzheimer's diseaseasymptomatic Alzheimer's diseasecognitiondementianeuropathologypathophysiologypost‐mortem examinationsystematic review

Identifiers

PMID42103686
PMCPMC13156076

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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.