Evidence map›Paper›PMID 41950067›Full record

ReviewAlzheimer's & dementia : the journal of the Alzheimer's Association2026

A perspective: PLA2G4A as drug target for vascular inflammation in Alzheimer's disease.

Ambreen Kanwal, Bilal E Kerman, Shaowei Wang, Kevin Camey, Boyang Li, Lisi Flores-Aguilar, Nada Ali, Laura Beth McIntire, Chang April Shu, Stan G Louie and 3 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. 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. A perspective: PLA2G4A as drug target for vascular inflammation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    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

13 authors.

Ambreen KanwalDepartment of Genetics, Washington University in Saint Louis, Saint Louis, Missouri, USA.ORCID 0000-0002-7969-0600
Bilal E KermanDepartment of Neurology, University of Southern California, Los Angeles, California, USA.ORCID 0000-0003-1106-3288
Shaowei WangDepartment of Neurology, University of Southern California, Los Angeles, California, USA.
Kevin CameyDepartment of Neurology, University of Southern California, Los Angeles, California, USA.
Boyang LiDepartment of Neurology, University of Southern California, Los Angeles, California, USA.
Lisi Flores-AguilarDepartment of Pathology & Laboratory Medicine, University of California, Irvine, California, USA.
Nada AliDepartment of Neurology, University of Southern California, Los Angeles, California, USA.
Laura Beth McIntireDepartment of Radiology, Brain Health Imaging Institute, Weill Cornell Medicine, New York, New York, USA.
Chang April ShuCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Stan G LouieAlfred E. Mann School of Pharmacy and Pharmaceutical Sciences University of Southern California, Los Angeles, California, USA.
Elizabeth HeadDepartment of Pathology & Laboratory Medicine, University of California, Irvine, California, USA.
Zoe ArvanitakisRush Alzheimer's Disease Center, Rush University, Chicago, Illinois, USA.
Hussein N YassineDepartment of Neurology, University of Southern California, Los Angeles, California, USA.

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHUI, HELENA CHANG · 1985 to 2019
$41.0M
USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI · 2020 to 2026
$27.8M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
The delivery of essential fatty acids to the Brain in Alzheimer's diseaseR01AG054434 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YASSINE, HUSSEIN N · 2017 to 2021
$5.4M
Biomarkers of ABCA1 mediated functions in Alzheimers diseaseR01AG055770 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YASSINE, HUSSEIN N · 2017 to 2021
$4.2M
Linking peripheral and brain insulin resistance to AD neuropathology and cognitionRF1AG059621 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI AHIMA, REXFORD S., ARNOLD, STEVEN E · 2018 to 2018
$3.8M
ApoE, ABCA1 and endosomal dysregulation in ADR01AG067063 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI YASSINE, HUSSEIN N · 2020 to 2024
$3.4M
Elucidating endolysosomal trafficking dysregulation induced by APOE4 in human astrocytesR01AG082362 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Julia TCW · 2023 to 2026
$3.3M
Spatial dysregulation of the lipidome in Alzheimers disease human and mouse brainR01AG078800 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI Laura Beth Johnson McIntire, Vilas Menon · 2022 to 2026
$3.3M
Drug Development for Alzheimer's neuroinflammationU01AG094622 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Kai Chen, VSEVOLOD KATRITCH · 2025 to 2026
$3.2M
Alzheimer's Drug Discovery Foundation (ADDF; GC-201711-2014197NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG066530NIA NIH HHS P30AG066530NIA NIH HHS P30 AG072975NIA NIH HHS P30AG10161NIA NIH HHS P30AG72975NIA NIH HHS P50 AG005142NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG054434NIA NIH HHS R01AG054434NIA NIH HHS R01 AG055770NIA NIH HHS R01AG055770NIA NIH HHS R01 AG067063NIA NIH HHS R01AG067063NIA NIH HHS R01 AG072794NIA NIH HHS R01AG072794NIA NIH HHS R01 AG074549NIA NIH HHS R01 AG078800NIA NIH HHS R01AG078800NIA NIH HHS R01 AG082362NIA NIH HHS R01AG082362NIA NIH HHS R01AG15819NIA NIH HHS R21 AG056518NIA NIH HHS R21AG056518NIA NIH HHS RF1 AG059621NIA NIH HHS RF1 AG076124NIA NIH HHS RF1AG076124NIA NIH HHS U01 AG094622NIH HHS P50AG05142NIH HHS R01AG074549NIH HHS RF1 AG059621Vranos and Tiny Foundations
6 · The paper itself

Abstract

Anti-amyloid therapies for Alzheimer's disease (AD) modestly slow cognitive decline but carry significant risk of amyloid-related imaging abnormalities (ARIAs), brain swelling, and hemorrhage, particularly in apolipoprotein E ε4 carriers. Cerebral amyloid angiopathy (CAA) and vascular inflammation drive this vulnerability, highlighting the need for complementary strategies targeting upstream mechanisms of vascular injury. Cytosolic phospholipase A2 (cPLA2) regulates arachidonic acid and lysophosphatidylcholine-derived lipid signaling at the intersection of amyloid burden, oxylipin dysregulation, blood-brain barrier disruption, and neurovascular inflammation. By depleting protective membrane plasmalogens while amplifying inflammatory lipid mediators, cPLA2 creates a state of vascular vulnerability predisposing to ARIAs. This Perspective article synthesizes evidence from human, preclinical, and translational studies positioning cPLA2 as an upstream driver of CAA-related inflammation and vascular vulnerability in AD. We discuss biomarker and imaging approaches to assess cPLA2 activity in vivo and outline how targeting this pathway may enhance anti-amyloid therapy safety by mitigating ARIA risk.

Indexed as

Alzheimer DiseaseCerebral Amyloid AngiopathyGroup IV Phospholipases A2InflammationAnimalsBrainHumansGroup IV Phospholipases A2Alzheimer's diseaseamyloidamyloid‐related imaging abnormalitiesapolipoprotein Ecerebral amyloid angiopathycytosolic phospholipase A2neuroinflammationphospholipasePLA2G4A

Identifiers

PMID41950067
PMCPMC13060764

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.