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Brain Pathol. 2017 Sep;27(5):612-626. doi: 10.1111/bpa.12428. Epub 2016 Oct 5.

FTDP-17 with Pick body-like inclusions associated with a novel tau mutation, p.E372G.

Author information

1
Department of Neurology, Mayo Clinic, Jacksonville, FL.
2
Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
3
Department of Neurology, Mayo Clinic, Rochester, MN.
4
Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN.
5
Department of Neurology, Weill Cornell Medicine, New York, NY.
6
Department of Neurology, University of Florida College of Medicine, Gainesville, FL.

Abstract

Mutations in microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Here, we describe a patient with FTDP-17 and a novel missense mutation in exon 13 of MAPT, p.E372G. We compare clinicopathologic features of this patient to two previously unreported patients with another exon 13 mutation, p.G389R. The patient with the p.E372G mutation was a 40-year-old man with behavioral variant frontotemporal dementia (bvFTD), who subsequently developed agrammatic speech and parkinsonism. One of the FTDP-17 patients with p.G389R mutation presented at age 24 with agrammatic variant of primary progressive aphasia, and subsequently behavioral dysfunction. The other presented at age 53 with bvFTD, followed by agrammatic speech and corticobasal syndrome. Neuropathologic features of FTDP-17 due to p.E372G were similar to those of p.G389R, including tau-immunoreactive Pick body-like neuronal inclusions and swollen, tapering thread-like processes in white matter immunoreactive for 3-repeat and 4-repeat tau. Biochemical analysis of insoluble tau showed similar isoform compositions in p.E372G and p.G389R. Functional studies of the p.E372G mutation showed marked increase in tau filament formation and its reduced ability to promote microtubule assembly. Together these findings indicate that p.E372G is a pathogenic MAPT mutation that causes FTDP-17 similar to p.G389R.

KEYWORDS:

FTDP-17; MAPT mutations; Pick's disease; frontotemporal dementia; primary progressive aphasia

PMID:
27529406
PMCID:
PMC5380645
[Available on 2018-09-01]
DOI:
10.1111/bpa.12428

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