Progression pattern of α-synuclein pathology in Lewy body disease

Koichi Wakabayashi

Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine

The histopathological hallmark of Lewy body disease (LBD) is the presence of fibrillar aggregates referred to as Lewy bodies (LBs), in which α-synuclein is a major constituent. LBs are widely distributed in the central nervous system, including the olfactory bulb. Similar inclusions are also found in the peripheral autonomic nervous system, including the sympathetic ganglia, enteric nervous system of the alimentary tract, heart and skin. Thus, LBD is a multisystem disorder including the peripheral nervous system. Recent studies have shown that proteinase K (PK)-resistant α-synuclein was deposited in LBs, as well as in the presynapses in distinct brain regions, including the hippocampus, temporal cortex and substantia nigra. Moreover, PK-resistant α-synuclein in the presynapse is non-fibrillar and not phosphorylated. PK-resistant α-synuclein may disturb the neurotransmission in LBD.

Address correspondence to Dr. Koichi Wakabayashi, Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine (5 Zaifu-cho, Hirosaki 036-8562, Japan)