Increased glucosylsphingosine levels and Gaucher disease in GBA1-associated Parkinson's disease.

INTRODUCTION: Gaucher's disease (GD) is caused by biallelic mutations in the GBA1 gene, leading to reduced glucocerebrosidase (GCase) activity and substrate (glucosylceramide and glucosylsphingosine, GlcSph) accumulation. GBA1 variant carriers are at risk of Parkinson's disease (PD), but only those with biallelic mutations cross the threshold of GCase reduction, leading to substrate accumulation and GD. The link between GBA1 mutations, GD and PD is not fully understood. Here we aimed at reporting the results of a large PD population screening with dried blood spot tests for GD. METHODS: We measured GCase activity and GlcSph levels in 1344 PD patients with dried blood spot tests, and performed GBA1 genetic sequencing. RESULTS: While the GCase activity was reduced in GBA1-PD carriers compared to wild type PD, GlcSph was increased in GBA1-PD compared to GBA1-controls, regardless of the underlying type of GBA1 variant. 13.6 % and 0.4 % of PD patients had mono- or biallelic GBA1 mutations respectively. GCase deficiency, lipid accumulation and clinical manifestations of GD was detected in five PD patients with biallelic GBA1 mutations, of whom four had a risk combined with a GD causing variant. CONCLUSIONS: GlcSph appearing higher in PD may represent a reliable biomarker of the disease and deserves to be further investigated. This study highlights the importance of screening PD patients for possible underlying GD, which is a treatable condition that should not be missed. We diagnosed GD cases carrying a "risk" variant in one allele, which is an unprecedented finding deserving further investigation.

Development and implementation of multicomponent homecare interventions for multimorbid and frail older people based on Information and Communication Technologies: The MULTIPLAT_AGE project.

The prevention and treatment of frailty condition among multimorbid older adults, in community and hospital settings, is becoming a healthcare priority. Growing evidence suggests that a multidimensional approach could help not only in the early identification of older patients' needs but also in designing personalized preventive interventions. However, in clinical practice, the effectiveness of such interventions is limited by a lack of continuity of care and poor compliance of patients. The widespread diffusion of the information and communication technology (ICT) could offer an excellent way to implement and monitor multidimensional and personalized interventions for multimorbid older adults. In this scenario, the MULTIPLAT_AGE, is a network project involving five research centers with the main objective to supply multidimensional interventions targeted to cognitive, motor, pharmacological, and functional domains including ICT-based: i) transitional care model from the hospital to a protected home area; ii) automatic home-care system to improve activities of daily living; iii) program to improve appropriate drug prescription in nursing-home residents; iv) tele-rehabilitation program to reduce the risk of falls and v) cognitive stimulation delivered by remote in older adults with neurological disorders. Each project is linked to the others by employing a shared online platform, in a perspective of technological-supplied multicomponent interventions according to the concept of "aging in place" as the best solution for the treatment and healthcare of older people. Here we describe the general framework of the MULTIPLAT_AGE, and we examine every single project, pointing out innovative aspects, and discussing the expected results.