CCR5 deficiency: Decreased neuronal resilience to oxidative stress and increased risk of vascular dementia.
Alzheimers Dement
; 20(1): 124-135, 2024 Jan.
Article
in En
| MEDLINE
| ID: mdl-37489764
ABSTRACT
INTRODUCTION:
As the chemokine receptor5 (CCR5) may play a role in ischemia, we studied the links between CCR5 deficiency, the sensitivity of neurons to oxidative stress, and the development of dementia.METHODS:
Logistic regression models with CCR5/apolipoprotein E (ApoE) polymorphisms were applied on a sample of 205 cognitively normal individuals and 189 dementia patients from Geneva. The impact of oxidative stress on Ccr5 expression and cell death was assessed in mice neurons.RESULTS:
CCR5-Δ32 allele synergized with ApoEε4 as risk factor for dementia and specifically for dementia with a vascular component. We confirmed these results in an independent cohort from Italy (157 cognitively normal and 620 dementia). Carriers of the ApoEε4/CCR5-Δ32 genotype aged ≥80 years have an 11-fold greater risk of vascular-and-mixed dementia. Oxidative stress-induced cell death in Ccr5-/- mice neurons.DISCUSSION:
We propose the vulnerability of CCR5-deficient neurons in response to oxidative stress as possible mechanisms contributing to dementia.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dementia, Vascular
/
Resilience, Psychological
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Alzheimers Dement
Year:
2024
Document type:
Article
Affiliation country: