Furthermore, while abnormal aggregation of αsyn is the dominant pathological hallmark of synucleinopathies, the nature of αsyn aggregation is distinct between different disorders. For example, PD, Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by αsyn deposits in neuronal Lewy bodies and Lewy neurites, whereas multiple system atrophy (MSA) is defined by abnormal filamentous deposition of αsyn in the nuclei and cytoplasm of both oligodendrocytes and neurons [70-72]. If prion-like αsyn seeding plays an important role in the pathogenesis of neurodegenerative disease then how and why αsyn behaves differently in different diseases must be addressed (see below).
A final challenge to the prion-like propagation of αsyn pathology accounting for PD is the observation that Lewy pathology is not necessary for nigral degeneration and the clinical presence of parkinsonism. While pathological studies on genetic forms of PD are limited, it is clear that at least some of these patients do not show classic Lewy pathology
https://pmc.ncbi.nlm.nih.gov/articles/PMC3776210/
Thus, it is vital that further in vitro and in vivo studies are performed to validate the potential involvement of αsyn as a prion-like factor and tease out the mechanisms by which αsyn may be responsible for disease progression in the human condition. However, in view of the unresolved challenges highlighted in this review, caution should be taken in uncritically accepting a role for a prion-like process, particularly in all cases of PD. Indeed, the mechanisms contributing to the progression of the disease may be as variable as the disease itself?