Tau and alpha-synuclein inclusions in a case of familial frontotemporal dementia and progressive aphasia.
Recent studies have shown that neurofibrillary tangles are frequently accompanied by alpha-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 alpha-synuclein pathology. The 2 patients' brains revealed abundant tau pathology in the hippocampus and basal ganglia, whereas tau and alpha-synuclein aggregates coexisted only in the nucleus basalis of Meynert, the only region where alpha-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, alpha-synuclein, beta-synuclein, or parkin genes. We think that this is the first report showing a specific colocalization of neurofibrillary tangles and Lewy bodies in a family with progressive aphasia.
Yancopoulou
Despina
D
Department of Clinical Neurosciences Brain Repair Center, University of Cambridge, Cambridge, UK.
Xuereb
John H
JH
Crowther
R Anthony
RA
Hodges
John R
JR
Spillantini
Maria Grazia
MG
D001037:Aphasia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western / Q000379:methods; D003704:Dementia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005192:Family Health; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C497604:SNCA protein, human; C497607:SNCB protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D016875:tau Proteins