Affiliations: Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Correspondence:
[*]
Corresponding author: Dr. Virginia M.-Y. Lee, Department of
Pathology and Laboratory Medicine, Center for Neurodegenerative
Disease Research, HUP, 3rd Floor Maloney Building, University of
Pennsylvania School of Medicine, 3600 Spruce Street, Philadelphia,
PA 19104, USA. Tel.: +1 215 662 6427; Fax: +1 215 349 5909;
E-mail: vmylee@mail.med.upenn.edu.
Abstract: The discovery that mutations within the tau gene lead to frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) provided direct evidence that tau alterations can lead to neurodegenerative disease. While the presence of tau fibrils and tangles is a common feature of all tauopathies, including Alzheimer's disease (AD), data are emerging from biochemical, cell-based and transgenic mouse studies which suggest that a pre-fibrillar form of pathological tau may play a key role in eliciting central nervous system neurodegeneration and behavioral impairments. Herein we review recent findings that implicate diffusible tau pathology in the onset of neurodegeneration, and discuss the implications of these findings as they relate to tau tangles and possible therapeutic strategies for the treatment of AD and related tauopathies.
