Neuropathology

Abstract

This research is based on the brain bank project, which combines prospective clinical follow ups and retrospective neuropathological studies. Pathology of idiopathic Parkinson disease (PD) can be summarized as a spectrum of Lewy body (LB) disease (LBD) comprising PD, dementia with LB (DLB) and pure autonomic failure (PAF). Recently core protein component of LB is proved to be alpha-synuclein, which is truncated, phosphorylated and ubiquitinated. Immunohistochemistry with anti-phosphorylated alpha-synuclein (psyn) antibody visualizes LB pathology with previously unattained high sensitivity and specificity, and enables pathological studies of peripheral autonomic nervous system as well as central nervous system. Recently Braak et al proposed ascending extension hypothesis of LB pathology, based on consecutive autopsy cases of PD and normal controls without dementia. However, not excluding demented cases, we found olfactory-amygdala extension pathway of LB pathology, which is independent from Braak's ascending pathway. We propose that abnormal seeding and aggregation of alpha-synuclein could be formed in peripheral autonomic nervous system or olfactory bulb and extend via neural network and form clinical phenotype of LBD.