Dataset Information

Proteomics of 2 postmortem Human Brain Regions for Identification of Cognitive Resilience Factors

ABSTRACT: We implemented an integrative systems-level analysis of multi-region postmortem human brain proteomics derived from the Religious Order and Rush Memory and Aging Project (ROSMAP) to identify proteins and pathways significantly altered in resilient cases. ROSMAP is an information-rich longitudinal cohort-based study in which participants enroll without dementia, undergo annual cognitive and clinical assessments and donate their brains at death (12). Multiplex tandem mass tag mass spectrometry (TMT-MS)-based proteomic data was implemented for a correlation network analysis. Data from an independent brain proteome wide association study (PWAS) of cognitive trajectory was integrated with the brain network to robustly prioritize protein communities associated with cognitive resilience. This revealed proteins linked to synaptic biology and cellular energetics. Neuritin (NRN1) was prioritized as a hub that co-expressed with a community of proteins with high correlation to cognitive stability in life and is known for important roles in synaptic maturation and stability.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Eric Dammer

LAB HEAD: Nicholas T. Seyfried, DPhil

PROVIDER: PXD040224 | Pride | 2023-07-20

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Search-PD_multiconsensus.zip	Other
	cgaiteri_26batchmulticoncensus.pdresult	Other
	cgaiteri_b01_01.raw	Raw
	cgaiteri_b01_02.raw	Raw
	cgaiteri_b01_03.raw	Raw

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Publications

Integrated Proteomics to Understand the Role of Neuritin (NRN1) as a Mediator of Cognitive Resilience to Alzheimer's Disease.

Hurst Cheyenne C Pugh Derian A DA Abreha Measho H MH Duong Duc M DM Dammer Eric B EB Bennett David A DA Herskowitz Jeremy H JH Seyfried Nicholas T NT

Molecular & cellular proteomics : MCP 20230405 5

The molecular mechanisms and pathways enabling certain individuals to remain cognitively normal despite high levels of Alzheimer's disease (AD) pathology remain incompletely understood. These cognitively normal people with AD pathology are described as preclinical or asymptomatic AD (AsymAD) and appear to exhibit cognitive resilience to the clinical manifestations of AD dementia. Here we present a comprehensive network-based approach from cases clinically and pathologically defined as asymptomat ...[more]

PMID: 37024090

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