PXD045403-1

PXD045403 is an original dataset announced via ProteomeXchange.

Title	AD-BXD Mouse PreFrontal Cortex Proteomics
Description	The AD-BXD mouse population is a powerful emerging model for studying AD resilience. AD-BXD mice query two different levels of genetic information: genometypes and genotypes. The genetically diverse BXD genometypes are a mosaic of the approximately 6 million segregating single nucleotide polymorphisms between C57BL/6J and DBA/2J mice. The transgenic genotype of the 5 times familial Alzheimer’s disease (5xFAD) transgene, which includes human APP carrying three pathogentic variants and human PSEN1 carrying two pathogenic, can be contrasted with non-transgenic control animals (Ntg). Reproducible BXD genometypes allow repeated measurement of the same mosaic genomes, a strategy that boosts the mappable heritability of genetic loci (cite ). This property facilitates QTL mapping of the relatively lower effect size variants that modify susceptibility to Alzheimer’s-like cognitive phenotypes in 5xFAD animals. Further, the same cognitive phenotype can be measured in both 5xFAD and Ntg mice within the same genometype. The ability to contrast a genometype’s performance with different AD genotypes facilitates the measurement of novel and interesting derived phenotypes based upon the property of trait correlation (cite ). Because of these properties, our lab has successfully leveraged AD-BXD mice to identify genetic modifiers of AD-related phenotypes in recent years. We quantified resilience using a novel regression-based metric. We utilized this measure to map resilience to a locus, then leveraged proteomics data to identify a putative molecular mechanism for the genetic resilience factor. We found potential novel targets for AD by querying elements coregulated in trans to the putative molecular mechanism. Finally, we implicated differential expression of networked synaptic proteins as the likeliest downstream consequences of differences in resilience.
HostingRepository	PanoramaPublic
AnnounceDate	2026-03-24
AnnouncementXML	Submission_2026-03-24_10:01:50.931.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Gennifer Merrihew
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Orbitrap Fusion; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-14 20:16:59	ID requested
⏵ 1	2026-03-24 10:01:51	announced

Chen Y, Stevenson TK, Cao Y, Fish LA, Robbins JE, Merrihew GE, Park J, Hohman TJ, MacCoss MJ, Kaczorowski CC, Genetic variation in the Nr1d1 transcription factor binding site shapes metabolism-related protein networks associated with cognitive resilience in an Alzheimer's disease mouse reference panel. Alzheimers Dement, 21(11):e70896(2025) [pubmed]

submitter keyword: DIA, Alzheimer's Disease, resilience, BXD genometypes

Michael MacCoss
contact affiliation	University of Washington
contact email	maccoss@uw.edu
lab head
Gennifer Merrihew
contact affiliation	University of Washington
contact email	genn@uw.edu
dataset submitter

Panorama Public dataset URI