title: Low CSF levels of both α-synuclein and the α-synuclein cleaving enzyme neurosin in patients with synucleinopathy.
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.
authors: Lund University, Department of Clinical Sciences Malmö, Molecular Memory Research Unit, The Wallenberg Laboratory at Skåne University Hospital, Malmö, Sweden.
authors: Malin
authors: M
authors: Wennström
authors: Yulia
authors: Y
authors: Surova
authors: Sara
authors: S
authors: Hall
authors: Christer
authors: C
authors: Nilsson
authors: Lennart
authors: L
authors: Minthon
authors: Fredrik
authors: F
authors: Boström
authors: Oskar
authors: O
authors: Hansson
authors: Henrietta M
authors: HM
authors: Nielsen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000134:cerebrospinal fluid*; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D051844:alpha-Synuclein; C103551:KLK6 protein, human; D007610:Kallikreins