Pathological findings in a patient with alpha-synuclein p.A53T and familial Parkinson's disease. (December 2020)

• Record Type: Journal Article
• Authors: Nishioka, Kenya; Hashizume, Yoshio; Takanashi, Masashi; Daida, Kensuke; Li, Yuanzhe; Yoshino, Hiroyo; Tambasco, Nicola; Prontera, Paolo; Hattori, Yuko; Ueda, Akihiro; Watanabe, Hirohisa; Hattori, Nobutaka
• Is Part Of: Parkinsonism & related disorders. Volume 81(2020)
• Page Start: 183
• Page End: 187
• Publication Date: 2020-12
• Subjects: Familial Parkinson's disease -- Pathology -- Alpha-synuclein -- Genetics; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2020.11.001
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: The present report documents a patient harboring an alpha-synuclein p.A53T variant from a family presenting with autosomal dominant inheritance, including four patients clinically diagnosed with Parkinson's disease (PD) and two with dementia. The alpha-synuclein p.A53T variant is linked to young- or middle-aged onset parkinsonism and cognitive decline. Our patient had a different haplotype from that of a patient with a p.A53T variant from an Italian family. The proband presented at 42 years of age with progressive parkinsonism and good response to levodopa in the early stages of the disease. At 46 years of age, he developed delusions and cognitive decline. Brain magnetic resonance imaging showed bilateral atrophic changes in the hippocampus and temporal lobes. He died of pneumonia at the age of 52 years. Neuropathological examination revealed severe neuronal loss in the substantia nigra, locus coeruleus, and dorsal nucleus of the vagus nerve, as well as widespread Lewy pathology including Lewy bodies and neurites, corresponding to Braak stage 6, and diffuse neocortical-type PD. There was mild appearance of tau pathology and glial cytoplasmic inclusion, in the absence of TDP-43 pathology. Alpha-synuclein p.A53T characteristically cause the Lewy body pathology and the symptoms, that resembled those of the reported patients with p.A53T. Highlights: We describe a case of patient with an alpha-synuclein p.A53T mutation. Widespread cortical Lewy bodies and diffuse neocortical-type PD were noted. Mild tau pathology and the absence of TDP-43 pathology were also noted.