Aggregation of misfolded proteins

According to the staging scheme of Braak and colleagues, the accumulation of aggregated α-synuclein that forms Lewy pathology is first seen in the lower parts of the brainstem during early PD, and then spreads over time in a relatively predictable way through different regions of the brain.² This phenomenon has been observed in the brain tissue of deceased patients with PD, yet the mechanisms by which this spreading occurs are not entirely certain.¹ However, a growing body of evidence has suggested that the α-synuclein proteins themselves may be responsible for the transmission of PD pathology from one area of the brain to another.⁴ This is known as the ‘prion model’ of disease transmission.⁴

References:
1.Hauser RA. α-Synuclein in Parkinson’s disease: getting to the core of the matter. Lancet Neurol 2015; 14 (8): 785–786.

2.Braak H, Ghebremedhin E, Rüb U, et al. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 2004; 318 (1): 121–134.

3.Woerman AL, Tamgüney G. Body-first Parkinson’s disease and variant Creutzfeldt-Jakob disease – similar or different? Neurobiol Dis 2022; 164: 105625.

4.Stopschinski BE, Diamond MI. The prion model for progression and diversity of neurodegenerative diseases. Lancet Neurol 2017; 16 (4): 323–332