Tau and alpha-synuclein inclusions in a case of familial frontotemporal dementia and progressive aphasia.

Abstract

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.

• Authors: Despina Yancopoulou, John H Xuereb, R Anthony Crowther, John R Hodges, Maria Grazia Spillantini
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 64 Issue 3 Pg. 245-53 (Mar 2005) ISSN: 0022-3069 [Print] England
• PMID: 15804056 (Publication Type: Case Reports, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nerve Tissue Proteins
• RNA, Messenger
• SNCA protein, human
• SNCB protein, human
• Synucleins
• alpha-Synuclein
• beta-Synuclein
• tau Proteins

Topics

• Aphasia (complications, metabolism, pathology)
• Blotting, Western (methods)
• Dementia (complications, metabolism, pathology)
• Family Health
• Humans
• Immunohistochemistry (methods)
• Lewy Bodies (metabolism, pathology, ultrastructure)
• Male
• Microscopy, Electron, Transmission (methods)
• Middle Aged
• Nerve Tissue Proteins (genetics, metabolism)
• Neurofibrillary Tangles (metabolism, pathology, ultrastructure)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Synucleins
• alpha-Synuclein
• beta-Synuclein
• tau Proteins (genetics, metabolism)