Clinicopathologic phenotypes of four cases with MAPT P301L mutation (P2.164)

OBJECTIVE: Hereditary tauopathy cases due to mutations in the microtubule-associated protein tau gene (MAPT) fall under the umbrella term of ‘frontotemporal dementia and parkinsonism linked to chromosome 17’ (FTDP-17). BACKGROUND: More than 40 different MAPT mutations have been identified, and the P301L mutation is the most common. DESIGN/METHODS: Genealogical, clinical, neuropathological, and genetic data were collected from four unrelated patients with previously-identified MAPT P301L mutation. RESULTS: were 3 males and one female. Mean age of death was 58.3 years (53-65 years), mean disease duration was 8.5 years (3-12 years). There was a positive family history of dementia in several relatives of all four The first symptoms included behavioral variant of frontotemporal dementia in three patients and Parkinsonism (tremor, bradykinesia) in one patient. MAPT haplotype data were available in two patients. One patient was homozygous for H1/H1 and the second patient was heterozygous for H1/H2. The mean brain weight was 1002.5 grams (880-1080 grams); lobar atrophy of frontotemporal distribution was present in all However, in three cases there was severe temporal cortical atrophy with relatively well-preserved hippocampus and amygdala and predominantly gray matter tau pathology. In the remaining case temporal atrophy was mild, and there were many globulhttp://files.abstractsonline.com/SUPT/146/1715/saveContinueButton.gifar glial inclusions in the white matter consistent with globular glial tauopathy (GGT). Immunohistochemistry was positive for 4Rtau in all cases. CONCLUSIONS: he MAPT P301L mutation may lead to different clinicopathologic phenotypes in unrelated patients. Besides cases with predominantly gray matter tau pathology, severe temporal cortical atrophy and absent or mild hippocampus and amygdala atrophy, this mutation can also lead to the GGT pathological phenotype. Study Supported by: NIH/NINDS P50 NS072187 and R01 NS078086, the NIH/NINDSP50 NS072187, the Michael J. Fox Foundation for Parkinson9s Research, and gift from Carl Edward Bolch, Jr., and Susan Bass Bolch, and Max Kade Foundation. Disclosure: Dr. Wszolek has received personal compensation in an editorial capacity for Parkinsonism u0026 Related Disorders and the European Journal of Neurology. Dr. Tacik has nothing to disclose. Dr. Sanchez Contreras has nothing to disclose. Dr. Wojtas has nothing to disclose. Dr. Ross has nothing to disclose. Dr. Fujioka has nothing to disclose. Dr. DeTure has nothing to disclose. Dr. Lin has nothing to disclose. Dr. Baker has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Strongosky has nothing to disclose. Dr. Kouri has nothing to disclose. Dr. Murray has nothing to disclose. Dr. Josephs has nothing to disclose. Dr. Rademakers has nothing to disclose. Dr. Ross has nothing to disclose. Dr. Dickson has nothing to disclose.