Isolated nigral degeneration without pathological protein aggregation in autopsied brains with LRRK2 p.R1441H homozygous and heterozygous mutations

Acta Neuropathologica Communications

Sho Tsuyama¹  Hiroshi Takashima²  Eiji Matsuura²  Masashi Takanashi³  Kenya Nishioka⁴  Yuanzhe Li⁴  Hiroyo Yoshino⁵  Nobutaka Hattori⁵  Manabu Funayama⁵ 

[1] Department of Human Pathology, Juntendo University School of Medicine;Department of Neurology and Geriatrics, Graduate School of Medical and Dental Sciences, Kagoshima University;Department of Neurology, Juntendo Koshigaya Hospital;Department of Neurology, Juntendo University School of Medicine;Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University;

关键词: LRRK2;    P.R1441H;    Parkinson’s disease;    Pathology;    Isolated nigral degeneration;    Makurazaki;   

DOI  :  10.1186/s40478-018-0617-y

来源: DOAJ

【 摘 要 】

Abstract Leucine-rich repeat kinase 2 (LRRK2) is the most common causative gene for autosomal dominant Parkinson’s disease (PD) and is also known to be a susceptibility gene for sporadic PD. Although clinical symptoms with LRRK2 mutations are similar to those in sporadic PD, their pathologies are heterogeneous and include nigral degeneration with abnormal inclusions containing alpha-synuclein, tau, TAR DNA-binding protein 43, and ubiquitin, or pure nigral degeneration with no protein aggregation pathologies. We discovered two families harboring heterozygous and homozygous c.4332 G > A; p.R1441H in LRRK2 with consanguinity, sharing a common founder. They lived in the city of Makurazaki, located in a rural area of the southern region, the Kagoshima prefecture, in Kyushu, Japan. All patients presented late-onset parkinsonism without apparent cognitive decline and demonstrated a good response to levodopa. We obtained three autopsied cases that all presented with isolated nigral degeneration with no alpha-synuclein or other protein inclusions. This is the first report of neuropathological findings in patients with LRRK2 p.R1441H mutations that includes both homozygous and heterozygous mutations. Our findings in this study suggest that isolated nigral degeneration is the primary pathology in patients with LRRK2 p.R1441H mutations, and that protein aggregation of alpha-synuclein or tau might be secondary changes.

【 授权许可】

Unknown