Evidence map›Paper›PMID 40665351›Full record

ArticleJournal of neuroinflammation2025

Ethanol consumption aggravates amyloid pathology and neuroinflammation in Alzheimer's disease associated with inflammasome activation and ASC speck propagation.

Veronika Brezani, Radhika S Joshi, Marti Ortega-Ribera, Prashanth Thevkar Nagesh, Viliam Brezani, Adam Zivny, Evelyn A Kurt-Jones, Douglas T Golenbock, Gyongyi Szabo

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Programmed cell death: a promising management for Alzheimer's disease.Apoptosis : an international journal on programmed cell death · 2026
    Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
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

9 authors.

Veronika BrezaniDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Radhika S JoshiDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Marti Ortega-RiberaDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Prashanth Thevkar NageshDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Viliam BrezaniDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Adam ZivnyDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Evelyn A Kurt-JonesDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Douglas T GolenbockDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Gyongyi SzaboDepartment of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. gszabo1@bidmc.harvard.edu.

Funding

MicroRNAs in Alcoholic Liver Disease Administrative SupplementR01AA020744 · NIAAA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SZABO, GYONGYI · 2011 to 2023
$5.3M
TLR4 Signaling in alcoholic liver diseaseR01AA017729 · NIAAA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SZABO, GYONGYI · 2009 to 2021
$4.3M
Inflammasome activation in modulation of Alzheimer’s Disease by alcohol Administrative SupplementR01AG072899 · NIA · BETH ISRAEL DEACONESS MEDICAL CENTER · PI GOLENBOCK, DOUGLAS T, SZABO, GYONGYI · 2020 to 2025
$2.4M
NIAAA NIH HHS 5R01AA017729NIAAA NIH HHS R01 AA017729NIAAA NIH HHS R01 AA020744NIA NIH HHS R01 AG072899NIH HHS 5R01AG072899
6 · The paper itself

Abstract

backgroundAlcohol use disorder (AUD) has been associated with Alzheimer's disease (AD) and dementia, yet the underlying mechanisms and specific role of ethanol in AD progression remain poorly understood. Neuroinflammation has emerged as a key contributor to both AD pathogenesis and ethanol-induced brain damage. Activation of innate immune cells and signaling pathways, in particular NLRP3 inflammasome, plays a pivotal role in both AD and ethanol-induced inflammation. Thus, we postulated that excessive ethanol consumption could contribute to AD progression via amplified neuroinflammation.

methodsThe 12-15-month-old WT and APP/PS1 mice received water or ethanol (3.5 g/kg) binge every alternate day for a period of one month. The effects of ethanol on amyloid pathology, microglia and astrocyte activation, and NLRP3 inflammasome activation were evaluated in the mouse brains. The effect of ethanol and amyloid β on NLRP3 inflammasome signaling was further studied in primary glial cells.

resultsIn this study, we show that repeated ethanol binges aggravate the amyloid pathology and plaque burden in the hippocampus of APP/PS1 mice. Furthermore, we demonstrate the additive effect of ethanol administration on NLRP3 inflammasome activation, IL-1β release, and ASC aggregation in the brains of APP/PS1 mice and primary glia cultures. Our study also reveals a strong astrocyte activation by ethanol in the hippocampus of APP/PS1 mice as demonstrated by significantly increased GFAP and ALDH1L1 protein levels. Further in vitro analysis revealed that ethanol potentiates the effect of amyloid β to increase the NLRP3 inflammasome activation in both primary astrocytes and microglia. Lastly, we demonstrate that glia-produced ASC specks induce IL-1β in microglia and astrocytes and induce ROS in SH-SY5Y neurons, contributing to sustained neuroinflammation in AD.

conclusionCollectively, our results demonstrate that ethanol consumption exacerbates features of AD pathology associated with amplified neuroinflammation and NLRP3/ASC inflammasome activation, which may play an important role in the disease progression and severity.

Indexed as

Alcohol DrinkingAlzheimer DiseaseCARD Signaling Adaptor ProteinsEthanolInflammasomesNeuroinflammatory DiseasesAmyloid beta-PeptidesAnimalsCentral Nervous System DepressantsMaleMiceMice, Inbred C57BLMice, TransgenicNLR Family, Pyrin Domain-Containing 3 ProteinAmyloid beta-PeptidesCARD Signaling Adaptor ProteinsCentral Nervous System DepressantsEthanolInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePycard protein, mouseAlcohol use disorderAlzheimer’sASC specksAstrocytesEthanolInflammasomeMicrogliaNeuroinflammation

Identifiers

PMID40665351
PMCPMC12265316

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.