Evidence map›Paper›PMID 40281298›Full record

ArticleMolecular neurobiology2025

Upregulation of NLRP3 Inflammasome in Specific Hippocampal Regions: Strengthening the Link Between Neuroinflammation and Selective Vulnerability in Alzheimer's Disease.

Eliana C B Toscano, Alberto F O Justo, Michelle C A Paula, Laura B Grossi, Vitor H Neves, Renata E P Leite, Vitor R Paes, Rossana C N Melo, Ricardo Nitrini, Carlos Pasqualucci and 4 more

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

14 authors.

Eliana C B ToscanoLaboratory of Pathology, Department of Pathology, Federal University of Juiz de Fora Medical School, Eugênio Do Nascimento, S/No.-Dom Bosco, Juiz de Fora, MG, 36038 - 330, Brazil. elianacbtoscano@gmail.com.ORCID http://orcid.org/0000-0002-8756-0689
Alberto F O JustoPhysiopathology in Aging Laboratory (LIM- 22), Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.
Michelle C A PaulaLaboratory of Pathology, Department of Pathology, Federal University of Juiz de Fora Medical School, Eugênio Do Nascimento, S/No.-Dom Bosco, Juiz de Fora, MG, 36038 - 330, Brazil.
Laura B GrossiLaboratory of Pathology, Department of Pathology, Federal University of Juiz de Fora Medical School, Eugênio Do Nascimento, S/No.-Dom Bosco, Juiz de Fora, MG, 36038 - 330, Brazil.
Vitor H NevesLaboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
Renata E P LeitePhysiopathology in Aging Laboratory (LIM- 22), Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.
Vitor R PaesPhysiopathology in Aging Laboratory (LIM- 22), Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.
Rossana C N MeloLaboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
Ricardo NitriniDepartment of Neurology, University of São Paulo Medical School, São Paulo, Brazil.
Carlos PasqualucciPhysiopathology in Aging Laboratory (LIM- 22), Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.
Eduardo FerriolliDivision of Geriatrics, Department of Internal Medicine, University of São Paulo Medical School, São Paulo, Brazil.
Antonio L 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, USA.
Lea T GrinbergMemory and Aging Center, University of California San Francisco, San Francisco, USA.
Claudia K SuemotoPhysiopathology in Aging Laboratory (LIM- 22), Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.

Funding

Fundação de Amparo à Pesquisa do Estado de São Paulo 20/14339-3Fundação de Amparo à Pesquisa do Estado de São Paulo 20/14350-7
6 · The paper itself

Abstract

Neuroinflammation has emerged as an important mechanism in the early stages of neurodegenerative diseases. Experimental models have demonstrated the detrimental role of inflammasomes in the development of Alzheimer's disease (AD). However, neuropathological studies characterizing NLRP1 and NLRP3 pathways in AD are scarce. In addition, the possible association between inflammasome-induced neuroinflammation and clinicopathological outcomes is unclear. This study aimed to characterize the hippocampal expression of the inflammasome proteins in post-mortem samples of individuals with pure AD neuropathological change (ADNC) compared to controls from an admixed Latin American sample (n = 28 per group). We also investigated potential associations of inflammasome expression with neuropathological burden and cognitive abilities. The expression of NLRP1, NLRP3, caspase-1, ASC, gasdermin D, IL-1β, IL-18, amyloid β, and hyperphosphorylated tau (p-tau) was evaluated in the cornu ammonis (CA), dentate gyrus (DG), and subiculum (SUB), using immunohistochemistry and morphometry. We also performed the alignment of serial sections and 3D reconstruction of ADNC samples to verify the spatial locations of NLRP3/ASC and AD pathology across the hippocampus. We used ordinal logistic regression to investigate potential associations between inflammasome proteins and AD pathology, while linear regression assessed relationships between inflammasome and cognitive abilities. NLRP3, ASC, caspase-1, IL-1β, and IL-18 were overexpressed in CA and SUB of individuals with ADNC compared to controls. NLRP3 pathway correlated with AD pathology and CDR-SB, mainly in CA and SUB. Our results suggest that hippocampal NLRP3, but not NLRP1, inflammasome was associated with pathologic burden and cognitive impairment in AD and may contribute to the selective vulnerability to AD pathology.

Indexed as

Alzheimer DiseaseHippocampusInflammasomesNeuroinflammatory DiseasesNLR Family, Pyrin Domain-Containing 3 ProteinUp-RegulationAgedAged, 80 and overFemaleHumansMaleInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanAD PathologyAlzheimer’s DiseaseHippocampusInflammasomeNLRP3

Identifiers

PMID40281298

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.