No abstract

Neurosin is a protease that in vitro degrades α-synuclein, the main constituent of Lewy bodies found in brains of patients with synucleinopathy including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Several studies have reported reduced cerebrospinal fluid (CSF) levels of α-synuclein in synucleinopathy patients and recent data also proposes a significant role of α-synuclein in the pathophysiology of Alzheimer's disease (AD). To investigate potential links between neurosin and its substrate α-synuclein in vivo we used a commercially available sandwich ELISA and an in-house developed direct ELISA to quantify CSF levels of α-synuclein and neurosin in patients diagnosed with DLB, PD and PD dementia (PDD) versus AD patients and non-demented controls. We found that patients with synucleinopathy displayed lower CSF levels of neurosin and α-synuclein compared to controls and AD patients. In contrast, AD patients demonstrated significantly increased CSF α-synuclein but similar neurosin levels compared to non-demented controls. Further, CSF neurosin and α-synuclein concentrations were positively associated in controls, PD and PDD patients and both proteins were highly correlated to CSF levels of phosphorylated tau in all investigated groups. We observed no effect of gender or presence of the apolipoprotein Eε4 allele on neither neurosin or α-synuclein CSF levels. In concordance with the current literature our study demonstrates decreased CSF levels of α-synuclein in synucleinopathy patients versus AD patients and controls. Importantly, decreased α-synuclein levels in patients with synucleinopathy appear linked to low levels of the α-synuclein cleaving enzyme neurosin. In contrast, elevated levels of α-synuclein in AD patients were not related to any altered CSF neurosin levels. Thus, altered CSF levels of α-synuclein and neurosin in patients with synucleinopathy versus AD may not only mirror disease-specific neuropathological mechanisms but may also serve as fit candidates for future biomarker studies aiming at identifying specific markers of synucleinopathy.

The primary aim of this study was to compare quality of life (QoL) in patients with Dementia with Lewy Bodies (DLB) and patients with Alzheimer disease (AD). The secondary aim of this study was to investigate determinants of QoL in DLB. Thirty-four patients with DLB at the Neuropsychiatry clinic, University Hospital MAS, Malmö, Sweden, were included in a cross-sectional study. These patients were matched to 34 patients with AD. Two QoL instruments, the EQ-5D instrument and the Quality of Life-Alzheimer disease (QoL-AD) instrument, were applied in this study. Both instruments were administered to both patients and caregivers. Patients with DLB in this study have significantly lower QoL than patients with AD regardless of instrument or whether patient or caregiver-reported QoL was used. Furthermore, this study shows that important determinants of QoL in DLB include Neuropsychiatric Inventory score, independency in instrumental activities of daily living, whether the patient is living with the caregiver and the presence of apathy and delusions.

DLB patients use more resources, and are more costly than AD patients. Dependency in instrumental activities of daily living is strongly correlated to resource use in DLB patients.