An autopsy case of type A FTLD‐TDP with a GRN mutation presenting with the logopenic variant of primary progressive aphasia at onset and with corticobasal syndrome subsequently

Author:

Tomenaga Takafumi1,Minatani Shinobu1,Namba Hiroto1,Takeda Akitoshi1,Yoshizaki Takahito1,Kawabe Joji2,Keyoumu Nazere3,Morino Hiroyuki3,Higuchi Makoto4,Matsubara Tomoyasu35ORCID,Hatsuta Hiroyuki16,Hasegawa Masato7ORCID,Murayama Shigeo58ORCID,Itoh Yoshiaki1ORCID

Affiliation:

1. Department of Neurology Osaka Metropolitan University Graduate School of Medicine Osaka Japan

2. Department of Nuclear Medicine Osaka Metropolitan University Graduate School of Medicine Osaka Japan

3. Department of Medical Genetics Tokushima University Graduate School of Biomedical Sciences Tokushima Japan

4. National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology Chiba Japan

5. Department of Neuropathology (Brain Bank for Aging Research) Tokyo Metropolitan Institute for Geriatrics and Gerontology Tokyo Japan

6. Hatsuta Neurology Clinic Osaka Japan

7. Department of Neuropathology and Cell Biology Tokyo Metropolitan Institute of Medical Science Tokyo Japan

8. Molecular Research Center for Children's Mental Development, United Graduate School of Child Development University of Osaka Osaka Japan

Abstract

A 68‐year‐old woman presented with difficulty finding words and writing characters. Neurological examination led to clinical diagnosis at onset of the logopenic variant of primary progressive aphasia accompanied with ideomotor apraxia, visuospatial agnosia on the right, and Gerstmann syndrome. Bradykinesia and rigidity on the right with shuffling gait developed after one year. Treatment with L‐dopa had no effect. The patient was diagnosed with corticobasal syndrome (CBS). Brain magnetic resonance imaging revealed diffuse cortical atrophy dominantly on the left, especially in the temporal, parietal, and occipital lobes. Positron emission tomography did not reveal any significant accumulation of amyloid β or tau protein. She died five years later. Neuropathological examination revealed diffuse cortical atrophy with severe neuronal loss and fibrous gliosis in the cortex. Neuronal cytoplasmic inclusions, short dystrophic neurites, and, most notably, neuronal intranuclear inclusions, all immunoreactive for phosphorylated TDP‐43, were observed. Western blotting revealed a full length and fragments of phosphorylated TDP‐43 at 45 and 23 kDa, respectively, confirming the pathological diagnosis of type A FTLD‐TDP. Whole exome sequencing revealed a pathogenic mutation in GRN (c.87dupC). FTLD‐TDP should be included in the differential diagnosis of CBS.

Funder

Japan Agency for Medical Research and Development

Japan Society for the Promotion of Science

Publisher

Wiley

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