PXD053491

PXD053491 is an original dataset announced via ProteomeXchange.

Title	Cortical region confers neuron-type-specific vulnerability to human APP expression
Description	Alzheimer’s Disease is a devastating and an irreversible neurodegenerative disease currently afflicting 50 million individuals worldwide, a number expected to escalate three-fold over the next 25 years. Preventative treatment is of dire importance, and yet, cellular mechanisms underlying early regional vulnerability in Alzheimer’s Disease remain unknown. In human patients with Alzheimer’s Disease, the earliest observed pathophysiological correlate to cognitive decline is hyperexcitability. In mouse models, early hyperexcitability has been shown in the cortical region first impacted by Alzheimer’s Disease. The origin of hyperexcitability in early stage-disease and why it preferentially emerges in specific regions is unclear. Using cortical-region and cell-type- specific proteomics and patch-clamp electrophysiology, we uncovered differential susceptibility to human-specific APP in a model of sporadic Alzheimer’s Disease. Shockingly, our findings reveal that early entorhinal hyperexcitability may result from intrinsic vulnerability of parvalbumin interneurons, prior to changes in surrounding excitatory neurons. This study suggests early disease interventions addressing non-excitatory cell-types may protect regions first vulnerable to pathological symptoms of Alzheimer’s Disease and downstream cognitive decline.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:47:49.289.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christina Ramelow
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-28 07:54:57	ID requested
1	2024-06-28 08:22:47	announced
⏵ 2	2024-10-22 06:47:49	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: APP

inhibition

PV interneuron

hyperexcitability

lateral entorhinal cortex

Alzheimer’s Disease

Matthew JM
contact affiliation	Department of Cell Biology, Emory University School of Medicine, Atlanta, GA, USA
contact email	mjrowan@emory.edu
lab head
Christina Ramelow
contact affiliation	Emory University
contact email	christinaramelow12@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD053491

PRIDE project URI

• PRIDE
  1. PXD053491
     1. Label: PRIDE project
     2. Name: Cortical region confers neuron-type-specific vulnerability to human APP expression