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

Kenya Nishioka; Yoshio Hashizume; Masashi Takanashi; Kensuke Daida; Yuanzhe Li; Hiroyo Yoshino; Nicola Tambasco; Paolo Prontera; Yuko Hattori; Akihiro Ueda; Hirohisa Watanabe; Nobutaka Hattori

doi:10.1016/j.parkreldis.2020.11.001

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

Parkinsonism Relat Disord. 2020 Dec:81:183-187. doi: 10.1016/j.parkreldis.2020.11.001. Epub 2020 Nov 4.

Authors

Affiliations

¹ Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. Electronic address: [email protected].
² Choju Medical Institute, Fukushimura Hospital, 19-14 Noyoricho, Yamanaka, Aichi, 441-8124, Japan.
³ Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
⁴ Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
⁵ Movement Disorders Center, Neurology Department, Santa Maria Della Misericordia Hospital, University of Perugia, Perugia, Italy.
⁶ Medical Genetics Unit, Santa Maria Della Misericordia Hospital, University of Perugia, Perugia, Italy.
⁷ Honmachi Neurological Clinic, 3-20-29 Sakae, Nakaku, Nagoya-shi, Aichi, 460-0008, Japan.
⁸ Department of Neurology, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
⁹ Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. Electronic address: [email protected].

PMID: 33171430
DOI: 10.1016/j.parkreldis.2020.11.001

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.

Keywords: Alpha-synuclein; Familial Parkinson's disease; Genetics; Pathology.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Autopsy
Female
Humans
Lewy Bodies / pathology
Male
Middle Aged
Parkinson Disease / genetics*
Parkinson Disease / pathology*
Pedigree
alpha-Synuclein / genetics*

Substances

SNCA protein, human
alpha-Synuclein