Functional Connectivity Analysis in Heterozygous Glucocerebrosidase Mutation Carriers


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Sezgin M., Kicik A., Bilgic B., Kurt E., Bayram A., Hanagası H. A., ...Daha Fazla

JOURNAL OF PARKINSONS DISEASE, cilt.11, sa.2, ss.559-568, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 11 Sayı: 2
  • Basım Tarihi: 2021
  • Doi Numarası: 10.3233/jpd-202295
  • Dergi Adı: JOURNAL OF PARKINSONS DISEASE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED)
  • Sayfa Sayıları: ss.559-568
  • Anahtar Kelimeler: Parkinson's disease, glucoserobrosidase, GBA, functional connectivity, resting state fMRI, STRIATAL CONNECTIVITY, PARKINSONS-DISEASE, RISK, REORGANIZATION, GENE
  • İstanbul Üniversitesi Adresli: Evet

Özet

Background: There is evidence that alterations in functional connectivity (FC) of the striatocortical circuits may appear before the onset of clinical symptoms of Parkinson’s disease (PD).
Objective: The aim of this studywas to investigate FC of the striatocortical circuitry in asymptomatic carriers of heterozygous glucocerebrosidase (GBA) mutations, which pose a significant risk for developing PD.
Methods: Twenty-one parents of confirmed Gaucher disease patients who were carrying heterozygous GBA mutations and 18 healthy individuals matched for age and gender were included. GBA mutation analysis was performed in all participants. Clinical evaluation included neurological examination, Mini Mental State Examination, and UPDRS Part III. Structural and functional MRI data of 18 asymptomatic GBA mutation carriers (asGBAmc) and 17 healthy controls (HC) were available. FC was analyzed with seed-based approach.
Results: Eleven asymptomatic mutation carriers had heterozygous p.L483P mutation, 6 subjects heterozygous p.N409S mutation and 1 subject heterozygous p.R392G mutation in GBA gene. Mini-Mental State Examination mean score was 28.77
(±1.16) and 29.64 (±0.70) in asGBAmc and HC groups, respectively (p = 0.012). Significant increased connectivity between left posterior putamen and the left postcentral gyrus was found in the asGBAmc group compared to HC, whereas left caudate showed hyper-connectivity with the right parietal operculum and right planum temporale (Familywise alpha<0.05, adjusted for cluster size).
Conclusion: Our results suggest that alterations in striatocortical FC can be detected in asymptomatic heterozygous GBA mutation carriers who are at risk of developing PD. These findings may provide insight into network changes during the asymptomatic phase of PD.