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Updated: Mar 16, 2026
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
FTDP-17 with Pick body-like inclusions associated with a novel tau mutation, p.E372G
Pawel Tacik1, Michael A DeTure2, Yari Carlomagno2
1Department of Neurology, Mayo Clinic, Jacksonville, 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.
Insights
A novel microtubule-associated protein tau (MAPT) mutation, p.E372G, causes frontotemporal dementia with parkinsonism (FTDP-17). This genetic mutation leads to increased tau filament formation and impaired microtubule assembly, similar to other known FTDP-17 mutations.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Mutations in the microtubule-associated protein tau gene (MAPT) are linked to frontotemporal dementia with parkinsonism (FTDP-17).
- Understanding novel MAPT mutations is crucial for diagnosing and treating FTDP-17.
Purpose of the Study:
- To characterize a novel MAPT mutation (p.E372G) in a patient with FTDP-17.
- To compare the clinicopathologic features and biochemical properties of the p.E372G mutation with a previously reported exon 13 mutation (p.G389R).
Main Methods:
- Clinical and neuropathologic assessment of patients with FTDP-17.
- Biochemical analysis of insoluble tau.
- Functional studies of tau protein in vitro.
Main Results:
- The patient with p.E372G presented with behavioral variant frontotemporal dementia, followed by parkinsonism and speech deficits.
- Neuropathology revealed tau-immunoreactive inclusions and white matter abnormalities similar to p.G389R.
- Functional studies demonstrated increased tau filament formation and reduced microtubule assembly promotion by the p.E372G mutation.
Conclusions:
- The p.E372G mutation in MAPT is pathogenic and causes FTDP-17 with clinical and neuropathologic features similar to the p.G389R mutation.
- This study expands the spectrum of MAPT mutations associated with FTDP-17 and highlights the role of tau pathology.
