Abstract
Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy are characterized by aggregation of abnormal α-synuclein (α-syn) and collectively referred to as α-synucleinopathy. Because these diseases have different prognoses and treatments, it is desirable to diagnose them early and accurately. However, it is difficult to accurately diagnose these diseases by clinical symptoms because symptoms such as muscle rigidity, postural dysreflexia, and dementia sometimes overlap among these diseases. The process of conformational conversion and aggregation of α-syn has been thought similar to that of abnormal prion proteins that cause prion diseases. In recent years, in vitro conversion methods, such as real-time quaking-induced conversion (RT-QuIC), have been developed. This method has succeeded in amplifying and detecting trace amounts of abnormal prion proteins in tissues and central spinal fluid of patients by inducing conversion of recombinant prion proteins via shaking. Additionally, it has been used for antemortem diagnosis of prion diseases. Recently, aggregated α-syn has also been amplified and detected in patients by applying this method and many clinical studies have examined diagnosis using tissues or cerebral spinal fluid from patients. In this review, we discuss the utility and problems of α-syn RT-QuIC for antemortem diagnosis of α-synucleinopathies.
Highlights
Α-Synucleinopathies (α-synucleinopathies) are disorders characterized by aggregation and deposition of α-synuclein (α-syn), which include Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA)
MSA patients present with autonomic symptoms such as dysuria, orthostatic hypotension (OH), and erectile dysfunction, and they are classified as MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonian features (MSA-P) (Gilman et al, 2008; Mitsui et al, 2015)
Because α-syn is a major component of LBs in PD/DLB patients and glial cytoplasmic inclusions (GCIs) in MSA patients (Spillantini et al, 1997; Wakabayashi et al, 1998), these diseases are unified under the concept of α-synucleinopathy
Summary
Α-Synucleinopathies (α-synucleinopathies) are disorders characterized by aggregation and deposition of α-synuclein (α-syn), which include Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Detection of abnormal aggregated α-syn in CSF of DLB patients by the RT-QuIC assay was first reported by Fairfoul et al (2016); this was followed by multiple clinical studies. In the first report of α-syn RT-QuIC, the authors investigated the amount of CSF used as the seed in pure DLB (n = 12) patients who were neuropathologically diagnosed in the OPTIMA cohort study compared with normal controls (Fairfoul et al, 2016).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
