Tau and α-Synuclein Inclusions in a Case of Familial Frontotemporal Dementia and Progressive Aphasia

Recent studies have shown that neurofibrillary tangles are frequently accompanied by α-synuclein inclusions in sporadic and familial Alzheimer disease, in Down syndrome, in progressive supranuclear palsy, and Parkinsonism dementia complex of Guam. Here we report the cases of 2 brothers with familial progressive aphasia who developed features of frontotemporal dementia with predominant tau pathology but also α-synuclein pathology. The 2 patients' brains revealed abundant tau pathology in the hippocampus and basal ganglia, whereas tau and α-synuclein aggregates coexisted only in the nucleus basalis of Meynert, the only region where α-synuclein was present. In this brain region, abundant Lewy bodies, Lewy neurites, and tau inclusions were found; the pathology was more abundant in the older than in the younger brother. Sarkosyl-insoluble tau extracted from brains of the 2 patients showed the presence of tau filaments that contained 3 major tau bands of 60, 64, and 68 kDa on Western blot analysis. These bands contained mainly tau with 3 and 4 repeats and no amino-terminal inserts and tau with 4 repeats and one amino-terminal insert. No mutations were identified in the tau, α-synuclein, β-synuclein, or parkin genes. We think that this is the first report showing a specific colocalization of neuro-fibrillary tangles and Lewy bodies in a family with progressive aphasia.