Degree of genetic liability for Alzheimer's disease associated with specific proteomic profiles in cerebrospinal fluid.
Alzheimer Disease
/ genetics
Amyloid Precursor Protein Secretases
/ cerebrospinal fluid
Amyloid beta-Peptides
/ cerebrospinal fluid
Chitinase-3-Like Protein 1
/ cerebrospinal fluid
Cognitive Dysfunction
/ genetics
Female
Genetic Association Studies
Humans
Male
Peptide Fragments
/ cerebrospinal fluid
Polymorphism, Single Nucleotide
Proteomics
Risk
Young Adult
alpha-Synuclein
/ cerebrospinal fluid
tau Proteins
/ cerebrospinal fluid
Alzheimer's disease (AD)
Cell adhesion molecules
Cerebrospinal fluid (CSF)
Complement cascades
Cytokines
Polygenic risk scores (PGRS)
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
06
11
2019
revised:
13
03
2020
accepted:
14
03
2020
pubmed:
21
4
2020
medline:
16
1
2021
entrez:
21
4
2020
Statut:
ppublish
Résumé
Genetic factors play a major role in Alzheimer's disease (AD) pathology, but biological mechanisms through which these factors contribute to AD remain elusive. Using a cerebrospinal fluid (CSF) proteomic approach, we examined associations between polygenic risk scores for AD (PGRS) and CSF proteomic profiles in 250 individuals with normal cognition, mild cognitive impairment, and AD-type dementia from the Alzheimer's Disease Neuroimaging Initiative. Out of 412 proteins, 201 were associated with PGRS. Hierarchical clustering analysis on proteins associated with PGRS at different single-nucleotide polymorphism p-value inclusion thresholds identified 3 clusters: (1) a protein cluster correlated with highly significant single-nucleotide polymorphisms, associated with amyloid-beta pathology and complement cascades; (2) a protein cluster associated with PGRS additionally including variants contributing to modest risk, involved in neural injury; (3) a protein cluster that also included less strongly associated variants, enriched with cytokine-cytokine interactions and cell adhesion molecules. These findings suggest that CSF protein levels reflect varying degrees of genetic liability for AD and may serve as a tool to investigate biological mechanisms in AD.
Identifiants
pubmed: 32307133
pii: S0197-4580(20)30091-9
doi: 10.1016/j.neurobiolaging.2020.03.012
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
CHI3L1 protein, human
0
Chitinase-3-Like Protein 1
0
Peptide Fragments
0
alpha-Synuclein
0
amyloid beta-protein (1-42)
0
tau Proteins
0
Amyloid Precursor Protein Secretases
EC 3.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
144.e1-144.e15Subventions
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : Medical Research Council
ID : 503480
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : N01AG12100
Pays : United States
Organisme : CIHR
Pays : Canada
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : Wellcome Trust
ID : 082604/2/07/Z
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG033193
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.