PXD057115

PXD057115 is an original dataset announced via ProteomeXchange.

Title	Age-related loss of large dendritic spines in the precuneus is statistically mediated by proteins which are predicted targets of existing drugs
Description	Preservation of dendritic spines is a putative mechanism of protection against cognitive impairment despite development of Alzheimer Disease (AD)-related pathologies. Aging, the chief late-onset AD risk factor, is associated with dendritic spine loss in select brain areas. However, no study to our knowledge has observed this effect in precuneus, an area selectively vulnerable to early accumulation of AD-related pathology. We therefore quantified dendritic spine density in precuneus from 98 subjects without evidence of neurocognitive decline, spanning ages 20-96, and found a significant negative correlation between age and large dendritic spine density. In these same subjects, we conducted liquid chromatography-tandem mass spectrometry of >5000 proteins and identified 203 proteins which statistically mediated the effect of age on large dendritic spine density. Using computational pharmacology, we identified 10 drugs which are predicted to target these mediators, informing future studies designed to test their effects on age-related dendritic spine loss and cognitive decline.
HostingRepository	PRIDE
AnnounceDate	2026-08-07
AnnouncementXML	Submission_2026-08-06_23:50:23.577.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD057115
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Matthew MacDonald
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-23 12:44:10	ID requested
⏵ 1	2026-08-06 23:50:24	announced

10.6019/PXD057115;

10.1038/s41380-024-02817-w;

Krivinko JM, Fan P, Sui Z, Happe C, Hensler C, Gilardi J, Ikonomovic MD, McKinney BC, Newman J, Ding Y, Wang L, Sweet RA, MacDonald ML, Age-related loss of large dendritic spines in the precuneus is statistically mediated by proteins which are predicted targets of existing drugs. Mol Psychiatry, 30(5):2059-2067(2025) [pubmed]

submitter keyword: proteomics, human, brain tissue, Alzheimer Disease, dendritic spines

Matthew MaDonald
contact affiliation	University of Pittsburgh Department of Psychiatry
contact email	mlmacdonald@gmail.com
lab head
Matthew MacDonald
contact affiliation	University of Pittsburgh
contact email	mlmacdonald@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057115
     1. Label: PRIDE project
     2. Name: Age-related loss of large dendritic spines in the precuneus is statistically mediated by proteins which are predicted targets of existing drugs