Abstract
The pathological hallmarks of Parkinson's disease (PD) are the progressive loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies (LBs) in remaining neurons. LBs primarily consist of aggregated α-Synuclein (α-Syn). However, accumulating evidence suggests that Tau, which is associated with tauopathies such as Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and argyrophilic grain disease, is also involved in the pathophysiology of PD. A genome-wide association study (GWAS) identified MAPT, the gene encoding the Tau protein, as a risk gene for PD. Autopsy of PD patients also revealed the colocalization of Tau and α-Syn in LBs. Experimental evidence has shown that Tau interacts with α-Syn and influences the pathology of α-Syn in PD. In this review, we discuss the structure and function of Tau and provide a summary of the current evidence supporting Tau’s involvement as either an active or passive element in the pathophysiology of PD, which may provide novel targets for the early diagnosis and treatment of PD.
Highlights
Parkinson’s disease (PD), one of the most common neurodegenerative diseases, is currently incurable
Cross-sectional analyses: -baseline cerebrospinal fluid (CSF) biomarker levels positively correlated with each other -baseline CSF phosphorylated Tau (p-Tau)/total Tau (t-Tau) and Aβ42 have borderline effects on the time to reach the endpoint Longitudinal analyses: -t-Tau and t-Tau/Aβ42 change rate are correlated with Unified Parkinson Disease Rating Scale (UPDRS) total, or motor scores change rate
Pathological and genetic evidence suggests that Tau plays an essential role in the pathogenesis of PD
Summary
Parkinson’s disease (PD), one of the most common neurodegenerative diseases, is currently incurable. A genome-wide association study (GWAS) identified MAPT, the gene encoding Tau, as a risk gene for PD (Edwards et al 2010; International Parkinson’s Disease Genomics Consortium et al 2017). Yamada and coworkers found that elevated neuronal activity increased α-Syn release (Yamada and Iwatsubo 2018) These results indicate that neuronal excitotoxicity plays a vital role in the pathophysiology of PD. Compta et al reported that MAPT rs242557 is associated with high CSF Tau levels and low Aβ levels in PD patients (Compta et al 2011a, b) Another gene-based and pathway-enrichment analysis suggested that MAPT is involved in the development of olfactory dysfunction, one of the most common nonmotor symptoms of PD, in older individuals (Dong et al 2015). It is speculated that pathological α-Syn and Tau can spread from the host to the graft in a cell-to-cell
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