Alpha‐synucleinopathy is associated with spinocerebellar ataxia type 2 with Parkinsonism

Abstract

Levodopa‐responsive Parkinsonism may be dominant phenotype of patients with SCA2. In general, they have a shorter abnormal expansion of CAG repeats (less than 39) in ATXN2 gene. The aim is to elucidate neuropathologic basis of this variant SCA2 from different Japanese families and give a new perspective on pathogenesis of SCA2 with Parkinsonism.Case 1: He was diagnosed as having Parkinson's disease at age 50. At age 65, he showed cerebellar ataxia and slow eye movement. Case 2: He developed unstable gait at age 40. In addition to the ataxia, he had rigidity, bradykinesia, stooped posture and freezing gait. Genetic analyses of ATXN2 showed an expanded CAG repeat with 22/38 (case 1) and 22/37 (case 2).Neuropathology: There is an atrophy of the pons and cerebellum. The most striking finding was the presence of α‐synuclein immunoreactive Lewy bodies (LBs) and neuritis (LNs) in the locus coeruleus, dorsal motor nucleus of vagus, basal nucleus of Meynert and amygdala. LBs and LNs were also seen in the substantia nigra. The distribution of Lewy pathology was consistent with stage 2 (case 1) and stage 3 (case 2) according to Braak's criteria. The 1C2 antibody depicted intranuclear immunopositive deposits in the various regions. In addition, α‐synuclein deposits were not seen in SCA2 cases without Parkinsonism.We conclude that α‐synucleinopathy is vital pathologic alterations of SCA2 with Parkinsonism. JSPS 19500311