Neuropathology of Frontotemporal Lobar Degeneration-Tau (FTLD-Tau)
A clinically and pathologically heterogeneous type of frontotemporal lobar degeneration has abnormal tau pathology in neurons and glia (FTLD-tau). Familial FTLD-tau is usually due to mutations in the tau gene (MAPT). Even FTLD-tau determined by MAPT mutations has clinical and pathologic heterogeneity. Tauopathies are subclassified according to the predominant species of tau that accumulates, with respect to alternative splicing of MAPT, with tau proteins containing three (3R) or four repeats (4R) of ~32 amino acids in the microtubule binding domain. In Pick's disease (PiD), 3R tau predominates, whereas 4R tau is characteristic of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Depending upon the specific mutation in MAPT, familial FTLD-tau can have 3R, 4R or a combination of 3R and 4R tau. PiD is the least common FTLD-tau characterized by neuronal Pick bodies in a stereotypic neuroanatomical distribution. PSP and CBD are more common than PiD and have extensive clinical and pathologic overlap, with no distinctive clinical syndrome or biomarker that permits their differentiation. Diagnosis rests upon postmortem examination of the brain and demonstration of globose tangles, oligodendroglial coiled bodies and tufted astrocytes in PSP or threads, pretangles and astrocytic plaques in CBD. The anatomical distribution of tau pathology determines the clinical presentation of PSP and CBD, as well as PiD. The basis for this selective cortical vulnerability in FTLD-tau is unknown.
KeywordsCorticobasal degeneration Corticobasal syndrome Frontotemporal lobar degeneration-tau Pick’s disease Progressive supranuclear palsy Richardson syndrome
The authors thank Virginia Philips, Linda Rousseau and Monica Castanedes-Casey for their expert technical assistance. We appreciate the gift of CP13 from Peter Davies, Albert Einstein College of Medicine. Most of the cases used in this study were donated to the Society of Progressive Supranuclear Palsy brain bank and generous donations of family members in this endeavor are greatly appreciated. This study was supported by NIH grants P50-NS72187, P50-AG25711, P50-AG16574, P01-AG17216, R01-AG37491 and R21 AG38736, as well as The Robert E. Jacoby endowment and the Mayo Foundation for Education and Research.
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