Ailesel Parkinson hastalığında serebral küçük damar hastalığı imzalarını keşfetmek.

Araştırma özeti

Aşağıdaki metin kaynak makalenin lisansı doğrulanmış orijinal özetidir. cc by

Familial Parkinson's disease (PD) and vascular parkinsonism (VP) present overlapping features and may co-exist. To investigate whether PD and VP may share a potential pathogenic link and to what extent white matter hyperintensities may influence PD phenotype, we used the modified Scheltens scale and presented a descriptive and exploratory analysis of the classic neuroradiological features of cerebral small vessel disease (cSVD) in the axial T2-FLAIR MRI sequences in a cohort of 104 familial PD and PD prodromal patients and 48 age-matched controls from the PPMI publicly available database. We next performed whole exome sequencing to examine the protein coding variability in the main PD-causing and risk genes (VPS35, DJ1, PINK1, ATP13A2, PRKN, SNCA, LRRK2, GBA, MAPT, LAMP3, STK39) in a cohort of 96 patients with familial cSVD and 243 elderly healthy individuals (HEX database). In this cohort, patients with familial and prodromal PD present a moderate burden of superficial frontal white matter hyperintensities (p-value = 3.46e-06, Bonferroni-corrected), linked to a mild reduction of motor and cognitive function and an increased LRRK2 p.G2019S and p.R1441C variant penetrance, and bilateral basal ganglia periventricular enlarged spaces (p-value = 2.64e-03, Bonferroni-corrected). Moreover, one-third of familial PD patients displayed a burden of lacunar thalamic strokes (p-value = 0.058), associated with a moderate hypokinetic-rigid syndrome. Finally, we report no known pathogenic coding variant in the main PD causative genes and risk factors in a cohort of 96 early-onset cSVD Caucasian patients. Our study adds to the understanding of potential cSVD hallmarks within this familial LRRK2, GBA and SNCA PD-PD prodromal cohort.

İlgili konular