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Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) due to microtubule‐associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy
Author(s) -
Tacik P.,
SanchezContreras M.,
DeTure M.,
Murray M. E.,
Rademakers R.,
Ross O. A.,
Wszolek Z. K.,
Parisi J. E.,
Knopman D. S.,
Petersen R. C.,
Dickson D. W.
Publication year - 2017
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12367
Subject(s) - tauopathy , frontotemporal dementia , tau protein , parkinsonism , pathology , atrophy , frontotemporal lobar degeneration , dementia , psychology , biology , alzheimer's disease , medicine , disease , neurodegeneration
Aim The p.P301L mutation in microtubule‐associated protein tau ( MAPT ) is a common cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP‐17 due to p.P301L mutation. Methods Genealogical, clinical, neuropathologic and genetic data were reviewed from eight individuals. Results The series consisted of five men and three women with an average age of death of 58 years (52–65 years) and average disease duration of 9 years (3–14 years). The first symptoms were those of behavioural variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ϵ3/ϵ3 in seven and ϵ3/ϵ4 in one. The average brain weight was 1015 g (876–1188 g). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, whereas there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas‐positive globular glial inclusions typical of globular glial tauopathy (GGT). Conclusions This clinicopathologic study shows inter‐ and intra‐familial clinicopathologic heterogeneity of FTDP‐17 due to MAPT p.P301L mutation, including GGT in one patient.