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A perspective: PLA2G4A as drug target for vascular inflammation in Alzheimer's disease
Kanwal A, Kerman BE, Wang S, Camey K, Li B, Flores-Aguilar L, Ali N, McIntire LB et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026-04-01
Topic: Amyloid, tau and blood-test diagnosis
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.
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APA 7th
Kanwal, A., Kerman, B. E., Wang, S., Camey, K., Li, B., Flores-Aguilar, L., et al. (2026). A perspective: PLA2G4A as drug target for vascular inflammation in Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.71320
Vancouver
Kanwal A, Kerman BE, Wang S, Camey K, Li B, Flores-Aguilar L, et al. A perspective: PLA2G4A as drug target for vascular inflammation in Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2026. doi:10.1002/alz.71320. PMID: 41950067.
BibTeX
@article{kanwal2026-41950067,
author = {Kanwal, A. and Kerman, B. E. and Wang, S. and Camey, K. and Li, B. and Flores-Aguilar, L. and Ali, N. and McIntire, L. B. and others},
title = {{A perspective: PLA2G4A as drug target for vascular inflammation in Alzheimer's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2026},
doi = {10.1002/alz.71320},
pmid = {41950067},
url = {https://doi.org/10.1002/alz.71320}
}
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Key findings
- 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.
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Study details
- Evidence strengthLow
How this study scored 50/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 29 of the 58 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41950067) |
| Free to read | 2 / 2 | Free to read |
| Points | 29 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 29 of the 58 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
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