Collectively these studies along with numerous in vitro and culture studies support the concept of αS pathology spread within the brain via a conformational templating mechanism.
Recent increasing evidence suggests that Parkinson's disease and MSA pathology spread throughout the nervous system in a spatiotemporal fashion, possibly by prion-like propagation of alpha-synuclein positive aggregates between synaptically connected areas.
Analysis of tau propagation in over 20 nuclei located anteriorly, posteriorly, ventrally or dorsally to the site of infusion provided conclusive evidence that tau pathology spread only to regions that were synaptically connected to the site of infusion (Fig. 5).
α-Synucleinopathies are progressive diseases and in recent years there have been increasing efforts to identify the mechanisms involved in intracerebral spread of pathology, as it is reasoned that therapies that could slow or halt pathology spread would likely be disease modifying.
Furthermore, extensive reviews of large cohorts of autopsied patients with PD/DLB have revealed that, for a significant percentage of patients, the distribution of α-synuclein pathology is not consistent with the Braak scheme of α-synuclein neuronal pathology spread [ 56- 58].
Braak and co-workers [ 5] suggested that Lewy pathology first develops in the olfactory bulb (OB), the anterior olfactory nucleus (AON), and in the dorsal motor nucleus of the vagus nerve, and based on neural connections to regions affected in later disease stages, they proposed that the pathology spread along protracted unmyelinated axons to interconnected regions.
Instead, they fear they are leaving their frailest citizens feeling isolated in an indifferent, money-driven marketplace, which is widely described as an American pathology spreading with globalization.
Recent findings that α-synuclein pathology spreads to implanted grafts, focused research efforts on this topic.
Antibody mappings of the whole rat brain showed differential gradients of Tau pathology spreading.
Neuropathological studies report that AD pathology spreads through the brain in a relatively predictable fashion [ 3].
