Japanese Familial Cases of Frontotemporal Dementia and Parkinsonism with N279K Tau Gene Mutation

Yuwa Oka; Hidemoto Saiki; Yasumasa Hashimoto; Yuta Terada; Takashi Nakamura; Takashi Ayaki; Satoshi Orimo; Sadayuki Matsumoto

doi:10.1002/mdc3.13100

Japanese Familial Cases of Frontotemporal Dementia and Parkinsonism with N279K Tau Gene Mutation

Mov Disord Clin Pract. 2020 Nov 3;8(1):126-132. doi: 10.1002/mdc3.13100. eCollection 2021 Jan.

Authors

Yuwa Oka¹, Hidemoto Saiki¹, Yasumasa Hashimoto^{1

2}, Yuta Terada^{1

3}, Takashi Nakamura^{1

4}, Takashi Ayaki³, Satoshi Orimo⁵, Sadayuki Matsumoto¹

Affiliations

¹ Department of Neurology Kitano Hospital, Tazuke Kofukai Medical Research Institute Osaka Japan.
² Department of Molecular Therapy National Center of Neurology and Psychiatry, National Institute of Neuroscience Kodaira Japan.
³ Department of Neurology Kyoto University Graduate School of Medicine Kyoto Japan.
⁴ Department of Neurology Osaka Saiseikai Nakatsu Hospital Osaka Japan.
⁵ Department of Neurology Kanto Central Hospital of the Mutual Aid Association of Public-School Teachers Tokyo Japan.

Abstract

Background: Mutations in the tau gene linked to chromosome 17 cause frontotemporal dementia and parkinsonism (FTDP-17).

Objective: This study presents 3 Japanese familial cases diagnosed with N279K tau gene mutation, including 1 autopsy-confirmed case.

Methods: We compared the clinical presentations, cognitive functions, and images between the 3 familial cases diagnosed with N279K mutation.

Results: All 3 patients presented symptoms in their early 40s. One patient showed severe cognitive dysfunction and died in his sixth year after onset. The remaining 2 cases presented with parkinsonism-dominant clinical features. Among the 2 cases, 1 presented the characteristic symptoms of progressive supranuclear palsy. The pathological features of the dementia-dominant case showed frontal and temporal lobe-dominant neuronal loss and gliosis. Tau-positive neuronal and glial inclusions were found throughout. Further, tufted astrocytes and globose tangles were present whereas there were no Pick bodies and astrocytic plaques, compatible with pathology-confirmed frontotemporal lobar degeneration (FTLD) -tau subtypes.

Conclusions: Patients with FTDP-17 can be classified into the following 2 major groups: dementia and parkinsonism-plus predominant phenotypes. Among our 3 cases, 1 showed dementia predominance whereas the other 2 showed parkinsonism predominance. Mutations in the microtubule-associated protein tau (MAPT) present with several pathological features. Clinically, our case presented a behavioral variant frontotemporal dementia (bvFTD). However, morphologically, the observed glial and neuronal pathology met the criteria for progressive supranuclear palsy (PSP). This study highlights the clinical heterogeneity within and between families with same MAPT mutation. Few pathologically confirmed PSP cases have been reported with mutations in MAPT.

Keywords: FTDP‐17, FTLD, parkinsonism, PSP, MAPT, N279K.