Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer's disease.
Aged
Aged, 80 and over
Algorithms
Alzheimer Disease
/ complications
Amyloid beta-Peptides
/ genetics
Biomarkers
Cognitive Dysfunction
/ diagnosis
Computational Biology
/ methods
Female
Gene Expression Profiling
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Male
Middle Aged
Models, Genetic
Multifactorial Inheritance
Phenotype
Time Factors
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 10 2021
06 10 2021
Historique:
received:
08
04
2021
accepted:
22
09
2021
entrez:
7
10
2021
pubmed:
8
10
2021
medline:
31
12
2021
Statut:
epublish
Résumé
Cognitive decline in early-stage Alzheimer's disease (AD) may depend on genetic variability. In the Swedish BioFINDER study, we used polygenic scores (PGS) (for AD, intelligence, and educational attainment) to predict longitudinal cognitive change (measured by mini-mental state examination (MMSE) [primary outcome] and other cognitive tests) over a mean of 4.2 years. We included 260 β-amyloid (Aβ) negative cognitively unimpaired (CU) individuals, 121 Aβ-positive CU (preclinical AD), 50 Aβ-negative mild cognitive impairment (MCI) patients, and 127 Aβ-positive MCI patients (prodromal AD). Statistical significance was determined at Bonferroni corrected p value < 0.05. The PGS for intelligence (beta = 0.1, p = 2.9e-02) was protective against decline in MMSE in CU and MCI participants regardless of Aβ status. The polygenic risk score for AD (beta = - 0.12, p = 9.4e-03) was correlated with the rate of change in MMSE and was partially mediated by Aβ-pathology (mediation effect 20%). There was no effect of education PGS on cognitive measures. Genetic variants associated with intelligence mitigate cognitive decline independent of Aβ-pathology, while effects of genetic variants associated with AD are partly mediated by Aβ-pathology.
Identifiants
pubmed: 34615922
doi: 10.1038/s41598-021-99310-z
pii: 10.1038/s41598-021-99310-z
pmc: PMC8494841
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19853Subventions
Organisme : Medical Research Council
ID : MR/K01417X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1001253
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L501542/1
Pays : United Kingdom
Organisme : Parkinson's UK
ID : G-0907
Pays : United Kingdom
Organisme : Parkinson's UK
ID : G-1307
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J004758/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0701075
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0901254
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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