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Where and how alpha‐synuclein pathology spreads in Parkinson’s disease:
Author(s) -
Wakabayashi Koichi
Publication year - 2020
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12691
Subject(s) - alpha synuclein , enteric nervous system , dorsal motor nucleus , olfactory bulb , pathology , central nervous system , medicine , brainstem , medulla oblongata , parkinson's disease , autonomic nervous system , neuroscience , spinal cord , nervous system , peripheral nervous system , efferent , anatomy , biology , disease , vagus nerve , heart rate , stimulation , blood pressure , afferent
In Parkinson’s disease (PD), neuronal alpha‐synuclein aggregates are distributed throughout the nervous system, including the brain, spinal cord, sympathetic ganglia, submandibular gland, enteric nervous system, cardiac and pelvic plexuses, adrenal medulla, and skin. Thus, PD is a progressive multiorgan disease clinically associated with various motor and nonmotor symptoms. The earliest PD‐related lesions appear to develop in the olfactory bulb, dorsal vagal nucleus, and possibly also the peripheral autonomic nervous system. The brain is closely connected with the enteric nervous system via axons of the efferent fibers of the dorsal nucleus of vagal nerve. Anatomical connections also exist between the olfactory bulb and brainstem. Accumulating evidence from experimental studies indicates that transneuronal propagation of misfolded alpha‐synuclein is involved in the progression of PD. However, it cannot be ruled out that alpha‐synuclein pathology in PD is multicentric in origin. Based on pathological findings from studies on human materials, the present review will update the progression pattern of alpha‐synuclein pathology in PD.