Abstract
The accumulation of α-synuclein aggregates is the hallmark of Parkinson’s disease, and more generally of synucleinopathies. The accumulation of tau aggregates however is classically found in the brains of patients with dementia, and this type of neuropathological feature specifically defines the tauopathies. Nevertheless, in numerous cases α-synuclein positive inclusions are also described in tauopathies and vice versa, suggesting a co-existence or crosstalk of these proteinopathies. Interestingly, α-synuclein and tau share striking common characteristics suggesting that they may work in concord. Tau and α-synuclein are both partially unfolded proteins that can form toxic oligomers and abnormal intracellular aggregates under pathological conditions. Furthermore, mutations in either are responsible for severe dominant familial neurodegeneration. Moreover, tau and α-synuclein appear to promote the fibrillization and solubility of each other in vitro and in vivo. This suggests that interactions between tau and α-synuclein form a deleterious feed-forward loop essential for the development and spreading of neurodegeneration. Here, we review the recent literature with respect to elucidating the possible links between α-synuclein and tau.
Highlights
Age-related neurodegenerative disorders like Alzheimer’s disease (AD) and Parkinson’s disease (PD) take an overwhelming toll on individuals and society [1]
This corroborates what has been observed in humans and reinforces the idea that the interplay between αsyn and tau are pivotal in the neurodegenerative process
Conclusions and future directions The overlap and numerous similarities between synucleinopathies and tauopathies suggest that therapeutic strategies that target common processes of tau and αsyn aggregation could benefit patients across a spectrum of neurodegenerative disorders, and may be relevant for the treatment of secondary symptoms such as cognitive impairment in PD or secondary parkinsonism in dementia
Summary
Age-related neurodegenerative disorders like Alzheimer’s disease (AD) and Parkinson’s disease (PD) take an overwhelming toll on individuals and society [1]. The concept of the existence of a continuum between pure synucleinopathies and tauopathies has emerged and is supported by clinical observations of a high comorbidity and overlap between neurodegenerative disorders (Figure 1), in particular between dementia and parkinsonism [9]. In this continuum theory, two proteins are central: tau and αsyn. Tauopathies and synucleinopathies are not restricted to pure AD and PD respectively, but rather encompass a variety of other disorders in which co-occurrence of tau and αsyn inclusions is frequent such as in PDD, DLB, Lewy body variant of AD (LBVAD), Guam-Parkinson-ALS dementia complex [15,16] and even Down’s syndrome [17] (Figure 1).
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