Evidence map›Paper›PMID 41708936›Full record

ArticleCommunications biology2026

Sex-dependent rescue of memory and synaptic deficits in AD model mice by increasing PSD-95 palmitoylation.

Yixing Du, Katie Prinkey, Andrew Q Pham, Amber Lawrence, Celeste Morales, Maureen Dinata, Marlenne Gutierrez, Ahmed Khalil, Medha Sharma, Robert A Rissman and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Yixing DuDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Katie PrinkeyDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Andrew Q Pham *Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Amber Lawrence *Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Celeste Morales *Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Maureen Dinata *Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Marlenne Gutierrez *Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Ahmed Khalil *Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9384-8390
Medha SharmaDepartment of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Robert A RissmanAlzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego, CA, USA.
Mehreen ManikkothDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Ian BaickDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Haritha KarthikeyanDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Kim DoreDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA. kdore@ucsd.edu.ORCID http://orcid.org/0000-0001-6263-367X

Funding

U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG067049
6 · The paper itself

Abstract

PSD-95, a major scaffolding protein, requires palmitoylation to remain at synapses where it plays critical roles in synaptic structure and function. Here, we show that PSD-95 palmitoylation is specifically reduced in the hippocampus of female Alzheimer's disease (AD) model mice. Accordingly, these mice have significant memory deficits that are not observed in male AD model mice. Systemic injections of Palmostatin B, a depalmitoylating enzyme inhibitor (including the one acting on PSD-95), rescues memory deficits in female AD model mice and restores PSD-95 palmitoylation levels. Importantly, both synaptic structure and function are impaired in female AD model mice, and these deficits are normalized in Palmostatin B injected animals. This drug has no effects on amyloid plaques or GFAP levels, indicating that the rescue of behavioral and synaptic deficits is not due to effects on plaque or astrogliosis related AD pathology. Our data instead suggest that the sex-dependent rescue we observe is mediated by the stabilization of small, vulnerable dendritic spines. This study demonstrates that increasing PSD-95 palmitoylation might be an effective way to protect synapses from AD pathology and therefore a promising therapy for AD.

Indexed as

Alzheimer DiseaseDisks Large Homolog 4 ProteinLipoylationMemoryMemory DisordersSynapsesAnimalsDendritic SpinesDisease Models, AnimalFemaleGuanylate KinasesHippocampusIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMiceDisks Large Homolog 4 ProteinDlg4 protein, mouseGuanylate KinasesIntracellular Signaling Peptides and ProteinsMembrane Proteins

Identifiers

PMID41708936
PMCPMC13031330

What Socratic holds

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LicenceCC BY
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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 Socratic graph.