Objective: To determinate the frequencies of lysosomal glucocerebrosidase (GBA) common mutations in a large sample of neurodegenerative diseases including Alzheimer Disease (AD), Lewy Body Dementia (LBD), Amyotrophic Lateral Sclerosis (ALS) compared to Parkinson’s Diseases (PD) and healthy controls.

Background: Mutations in the gene GBA increase the risk of Parkinson’s Disease (PD). GBA variants predict a more rapid progression of cognitive dysfunction in parkinsonian patients. However, the precise frequencies of GBA mutations in other dementias and neurodegenerative disorders is still unclear.

Methods: We selected cohorts of unrelated consecutive patients with clinical diagnosis of neurodegenerative disorders including 139 PD, 144 AD, 48 LBD, 149 ALS and 200 healthy age- and ethnic-matched controls. The clinical diagnosi of AD was supported by the low level of beta amyloid in CSF. DNA was extracted from all patients in order to screen for selected mutations in GBA gene by specific amplification of a fragment including exons 8-11 followed by Taqman assay detecting the following variants: p.N380S, p. E326K, p. L444P and p. D409H. All samples resulted positive for these mutations were confirmed by Sanger sequencing.

Results: The preliminary screening revealed in PD patients a frequency of 2.16% for p.N370S, 1.44% for p.L444P and 2,88% for p.E326K. Among ALS, p.L444P and p.E326K where found in 0,67% of patients each, while both variants were rare among AD patients.

Conclusions: The ongoing study suggests that the most common GBA variants associated with PD are rare in patients clinically diagnosed with AD. Further analysis, including screening of N370S and D409H in all samples and screening of DLB and CTR, will reveal the possible association of these mutation with other forms of neurodegeneration.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/glucocerebrosidase-mutations-in-neurodegenerative-disorders-other-than-parkinsons-disease/