Genetics Contributes to Concomitant Pathology and Clinical Presentation in Dementia with Lewy Bodies.
J Alzheimers Dis
; 83(1): 269-279, 2021.
Article
em En
| MEDLINE
| ID: mdl-34308904
ABSTRACT
BACKGROUND:
Dementia with Lewy bodies (DLB) is a complex, progressive neurodegenerative disease with considerable phenotypic, pathological, and genetic heterogeneity.OBJECTIVE:
We tested if genetic variants in part explain the heterogeneity in DLB.METHODS:
We tested the effects of variants previously associated with DLB (near APOE, GBA, and SNCA) and polygenic risk scores for Alzheimer's disease (AD-PRS) and Parkinson's disease (PD-PRS). We studied 190 probable DLB patients from the Alzheimer's dementia cohort and compared them to 2,552 control subjects. The p-tau/Aß1-42 ratio in cerebrospinal fluid was used as in vivo proxy to separate DLB cases into DLB with concomitant AD pathology (DLB-AD) or DLB without AD (DLB-pure). We studied the clinical measures age, Mini-Mental State Examination (MMSE), and the presence of core symptoms at diagnosis and disease duration.RESULTS:
We found that all studied genetic factors significantly associated with DLB risk (all-DLB). Second, we stratified the DLB patients by the presence of concomitant AD pathology and found that APOE É4 and the AD-PRS associated specifically with DLB-AD, but less with DLB-pure. In addition, the GBA p.E365K variant showed strong associated with DLB-pure and less with DLB-AD. Last, we studied the clinical measures and found that APOE É4 associated with reduced MMSE, higher odds to have fluctuations and a shorter disease duration. In addition, the GBA p.E365K variant reduced the age at onset by 5.7 years, but the other variants and the PRS did not associate with clinical features.CONCLUSION:
These finding increase our understanding of the pathological and clinical heterogeneity in DLB.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
/
Proteínas tau
/
Doença por Corpos de Lewy
/
Doença de Alzheimer
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
/
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Holanda