Daniel Offen, Israel
Tel Aviv University Sackler Faculty of MedicineAuthor Of 1 Presentation
CSF-DERIVED EXOSOMES FROM PATIENTS WITH PARKINSON'S DISEASE INDUCE PARKINSON-LIKE SYMPTOMS AND PATHOLOGY
Abstract
Aims
Parkinson’s disease (PD) is characterized by the gradual appearance of intraneuronal Lewy aggregates (Lewy bodies), which are primarily composed of misfolded α-synuclein (α-syn), resulting in cytotoxicity and neural death. Recent studies support the idea of transcellular spread of misfolded α-syn in a prion-like transmission via exosomes secretion and induce pathological aggregates in healthy neurons. Indeed, exosomes derived from brain lysates and cerebrospinal fluid (CSF) of PD patients have been shown to propagate α-syn aggregation in healthy cells. Braak et al hypothesized the olfactory bulb as primary propagation site for the initiation of the disease. In the current study we examined whether aggregated α-syn can actively spread from the nasal cavity to the brain via exosomes and initiate pathological aggregate in the brain.
Methods
Healthy 2-months old C57/Bl mice were given exosomes isolated from patient's CSF, PD or non synucleinopathy disorders, by internasal administration, and three months after treatment, mice were subjected to behavior tests.
Results
CSF-derived exosomes from PD patients induced aggregation of α-syn in a neuroblastoma cell line as can be seen by positive Thioflavins staining. Importantly, internasal delivery of CSF-derived exosomes from PD patients into the nasal cavity of healthy wild type mice induced PD-like symptoms including impairments in motor function, hyposmia and elevated anxiety, compared to Non-PD treated and healthy untreated mice.
Conclusions
Our data suggests that CSF-derived exosomes from PD patients are sufficient for propagating α-syn aggregation in cell culture and initiating PD-like symptoms in healthy mice after internasal delivery.