PXD074065-1

PXD074065 is an original dataset announced via ProteomeXchange.

Title	Membrane Proteome Remodeling in Female APP Mice Following Muscarinic Acetylcholine Receptor M1 Modulation Revealed by Peptidisc Enabled DIA-MS
Description	Alzheimer’s disease (AD) is linked to profound dysregulation of membrane-embedded and membrane-associated proteins that govern amyloid processing, synaptic signaling, and neuronal communication. Yet most proteomic analyses prioritize soluble fractions, resulting in systematic underrepresentation of integral membrane proteins and limited access to disease-relevant membrane pathways. Here, we use a membrane-mimetic, data-independent acquisition proteomic workflow to define disease- and drug-induced remodeling of the cortical membrane proteome in an APP mouse model of Alzheimer’s disease. Female B6C3F1/J mice were aged to 9 months and treated for 8 weeks with or without the M1 muscarinic acetylcholine receptor positive allosteric modulator VU0486846. APP pathology drove a pronounced, genotype-specific remodeling of the membrane proteome, with enrichment of multiple membrane proteins linked to AD, including RyR2, PLD3, ITM2C, and CNTNAP2. In contrast, wild-type mice cortical membranes were enriched for membrane proteins involved in axon guidance and synaptic organization, such as EPHA5 and ROBO2. Activation of M1 using the VU0486846 produced minimal membrane proteome changes in wild-type mice but selectively enriched proteins involved in neuronal trafficking and synaptic plasticity in APP mice, including SORCS2, PLXND1, and CADM1. Together, these findings demonstrate that AD-associated proteomic remodeling is strongly concentrated at the membrane level and that M1 receptor activation preferentially engages disease-altered membrane networks rather than inducing widespread proteomic changes. This work establishes peptidisc-enabled membrane proteomics as a powerful approach for identifying membrane-associated biomarkers and evaluating therapeutic target engagement in AD.
HostingRepository	PRIDE
AnnounceDate	2026-07-10
AnnouncementXML	Submission_2026-07-10_12:04:04.814.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ashim Bhattacharya
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monomethylated residue; acetylated residue; deamidated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-04 16:04:35	ID requested
⏵ 1	2026-07-10 12:04:05	announced
2	2026-07-10 12:05:37	announced	2026-07-10: Updated project metadata.

Bhattacharya A, Antony F, Aoki H, Babu M, Ferguson SSG, Abd-Elrahman KS, Duong van Hoa F, Membrane Proteome Remodeling in Female APP/PS1 Mice Following M1 Muscarinic Receptor Modulation Revealed by Peptidisc-Enabled DIA-MS. J Proteome Res, 25(6):3136-3148(2026) [pubmed]

10.1021/acs.jproteome.6c00140;

submitter keyword: Membrane Mimetics, data independent acquisition, mus musculus, membrane proteome profiling, APP,Alzheimer's, Peptidisc

Ashim Bhattacharya
contact affiliation	Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of British Columbia
contact email	fduong@mail.ubc.ca
lab head
Ashim Bhattacharya
contact affiliation	University of British Columbia
contact email	ashim938@student.ubc.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD074065
     1. Label: PRIDE project
     2. Name: Membrane Proteome Remodeling in Female APP Mice Following Muscarinic Acetylcholine Receptor M1 Modulation Revealed by Peptidisc Enabled DIA-MS