Tau in the Pathophysiology of Parkinson’s Disease

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.

De novo missense variants in the PPP2R5D gene associated with Parkinson's disease in Chinese Han population

“…Increased activity of PP2A activates tyrosine hydroxylase and, consequently, dopamine synthesis [12]. Knocking out the PPP2R5D gene in mice leads the microtubule-associated protein tau to become progressively phosphorylated [13]; such tau can aggregate in PD, either contributing to the disease or simply re ecting its progression [14]. Our study justi es further research into the mechanisms behind the apparent association between PPP2R5D and PD.…”

Tau and Amyloid-β Peptides in Serum of Patients With Parkinson's Disease: Correlations With CSF Levels and Clinical Parameters

“…In patients with AD, increase in serum tau has been linked to cognitive deterioration and structural changes in many brain areas (17), while clinical correlations of increased blood tau in patients with PD are not established yet. However, higher CSF levels of tau proteins in PD have been measured in patients with cognitive decline (21) or greater brain network disruption (21)(22)(23). Accordingly, because of the correlation between serum and CSF t-tau, we could suppose that increase of serum t-tau in patients with PD can reflect widespread degeneration, with subsequent cognitive involvement.…”

Mitochondria-Microbiota Interaction in Neurodegeneration

“…Yet all three amyloids, and additional ones besides, can trigger one another’s aggregation, and mixed neurodegenerative disease is quite common ( Nguyen et al, 2021 ). Alpha-synuclein, for example, contributes to the aggregation of beta-amyloid and tau compounds, tau compounds contribute to the aggregation of alpha-synuclein ( Pan et al, 2021 ), and Lewy bodies have been observed not just in Parkinson’s but in other neurodegenerative disease as well ( Bendor et al, 2013 ; Wong and Krainc, 2017 ). Moreover, besides alpha-synuclein, Lewy bodies can contain tau and be surrounded by tau fibrils ( Pan et al, 2021 ).…”

“…Alpha-synuclein, for example, contributes to the aggregation of beta-amyloid and tau compounds, tau compounds contribute to the aggregation of alpha-synuclein ( Pan et al, 2021 ), and Lewy bodies have been observed not just in Parkinson’s but in other neurodegenerative disease as well ( Bendor et al, 2013 ; Wong and Krainc, 2017 ). Moreover, besides alpha-synuclein, Lewy bodies can contain tau and be surrounded by tau fibrils ( Pan et al, 2021 ). And conversely, besides beta-amyloid, plaques typically contain other amyloids ( D’Andrea and Nagele, 2010 ), including alpha-synuclein ( Bendor et al, 2013 ; Jankovska et al, 2021 ).…”

“…And conversely, besides beta-amyloid, plaques typically contain other amyloids ( D’Andrea and Nagele, 2010 ), including alpha-synuclein ( Bendor et al, 2013 ; Jankovska et al, 2021 ). In addition, the MAPT gene, which expresses tau, is implicated in not only Alzheimer’s ( Zhou and Wang, 2017 ) but also Parkinson’s ( Pan et al, 2021 ). It might thus be a mistake to treat the various degenerative diseases of the brain and body as categorically distinct rather than as interrelated (see also Nguyen et al, 2021 ).…”