Evidence map›Paper›PMID 41680938›Full record

ArticleActa neuropathologica communications2026

Evidence for cPLA2 activation in Alzheimer's disease synaptic pathology.

Qiu-Lan Ma, Brandon Ebright, Boyang Li, Jing Li, Jasmin Galvan, Ashley Sanchez, Michael Renteln, Dante Dikeman, Shaowei Wang, Bilal E Kerman and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Qiu-Lan MaKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA. qiulanma@usc.edu.
Brandon EbrightMann School of Pharmacy, University of Southern California, 1985 Zonal Ave, Los Angeles, CA, 90033, USA.
Boyang LiKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Jing LiKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Jasmin GalvanKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Ashley SanchezKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Michael RentelnKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Dante DikemanMann School of Pharmacy, University of Southern California, 1985 Zonal Ave, Los Angeles, CA, 90033, USA.
Shaowei WangKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Bilal E KermanKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Xinhui WangKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Marina ManvelianKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Xiaohui YuMann School of Pharmacy, University of Southern California, 1985 Zonal Ave, Los Angeles, CA, 90033, USA.
Paul SeidlerMann School of Pharmacy, University of Southern California, 1985 Zonal Ave, Los Angeles, CA, 90033, USA.
Berenice Gutierrez-GrebenkovaMitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA.
Brooke E HjelmKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Debra HawesKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Anne E HinikerKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Kyle M HurthKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, 600 S., Paulina St, Chicago, IL, 60612, USA.
Stan G LouieKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Helena C ChuiKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA.
Agenor LimonMitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA.
Zoe ArvanitakisRush Alzheimer's Disease Center, Rush University Medical Center, 600 S., Paulina St, Chicago, IL, 60612, USA.
Hussein N YassineKeck School of Medicine, University of Southern California, 1501 San Pablo St, Los Angeles, CA, 90033, USA. hyassine@usc.edu.

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · RUSH UNIVERSITY MEDICAL CENTER · 1991 to 2005
$10.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI DAVID ALAN BENNETT · 1998 to 2024
$6.0M
Research Education Component (REC)P30AG066530 · UNIVERSITY OF SOUTHERN CALIFORNIA · 2025 to 2025
$4.8M
Rush Alzheimer's Disease Research CenterP30AG072975 · RUSH UNIVERSITY MEDICAL CENTER · 2025 to 2025
$3.1M
Drug Development for Alzheimer's neuroinflammationU01AG094622 · UNIVERSITY OF SOUTHERN CALIFORNIA · 2025 to 2025
$1.5M
Elucidating endolysosomal trafficking dysregulation induced by APOE4 in human astrocytesR01AG082362 · BOSTON UNIVERSITY MEDICAL CAMPUS · 2025 to 2025
$810k
Brain cPLA2 as a mechanism for neuroinflammation in AD/ADRD with and without APOE4R01AG076124 · UNIVERSITY OF SOUTHERN CALIFORNIA · 2025 to 2025
$781k
Mechanisms of Synaptic Protection in Cognitive Resilence to Alzheimer's Disease NeuropathologyR01AG070255 · UNIVERSITY OF TEXAS MED BR GALVESTON · 2025 to 2025
$434k
NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG066530NIA NIH HHS P30AG066530NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG070255NIA NIH HHS R01AG070255NIA NIH HHS R01 AG076124NIA NIH HHS R01AG082362NIA NIH HHS U01 AG094622
6 · The paper itself

Abstract

Synaptic integrity is essential for learning and memory, and its loss is a strong predictor of cognitive decline in Alzheimer’s disease (AD). Although synaptic degeneration has been linked to excitotoxicity, neuroinflammation, and amyloid-β (Aβ) and tau pathology, the underlying mechanisms remain unclear. We investigated whether calcium-dependent cytosolic phospholipase A2 (cPLA2), an enzyme that releases arachidonic acid from membrane phospholipids, contributes to synaptic loss in AD. cPLA2 isoforms were quantified in synaptosomes isolated from postmortem frontal cortex of individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD dementia from the Religious Orders Study, and in human iPSC-derived neurons exposed to Aβ42 oligomers. Both cPLA2α and cPLA2β were elevated in AD synaptosomes and correlated with postsynaptic protein PSD-95, but not presynaptic markers. cPLA2β levels were strongly associated with cognitive dysfunction, particularly in males, and synaptosomal eicosanoids were increased and correlated with cPLA2. In iPSC-derived neurons, Aβ42 oligomers activated cPLA2α, promoted its phosphorylation and translocation to postsynaptic compartments, and induced PSD-95 loss—effects prevented by the selective cPLA2 inhibitor BRI-50460. These findings implicate cPLA2 overactivation in excitatory synaptic pathology and cognitive decline in AD, highlighting cPLA2 as a potential disease-modifying therapeutic target.

Indexed as

Alzheimer DiseaseGroup IV Phospholipases A2SynapsesAgedAged, 80 and overAmyloid beta-PeptidesCognitive DysfunctionDisks Large Homolog 4 ProteinFemaleFrontal LobeHumansInduced Pluripotent Stem CellsMaleNeuronsPeptide FragmentsSynaptosomesAmyloid beta-Peptidesamyloid beta-protein (1-42)Disks Large Homolog 4 ProteinGroup IV Phospholipases A2Peptide Fragments

Identifiers

PMID41680938
PMCPMC12998354

What Socratic 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 Socratic graph.