Progress from Alzheimer's tangles to pathological tau points towards more effective therapies now.
The landmark description of neurofibrillary tangles (NFTs) and senile plaques as the pathological hallmarks of an unusual form of dementia 100 years ago by Alois Alzheimer launched the quest to understand a neurodegenerative disorder that now has become a scourge in the 21st Century due to the unprecedented increase in human life expectancy since 1900. Indeed, while there are many benefits to individuals and society as a whole that will accrue from the remarkable gains in longevity since 1900, the risk of developing Alzheimer's disease (AD) increases exponentially with advancing age beyond the 7th decade of life. Hence, the prevalence of AD will rise inexorably in the coming decades unless effective interventions are developed to delay the onset or progression of AD. Widespread international recognition of the urgency of this problem has accelerated research to discover meaningful therapies for AD, and growing evidence implicates impairments of axonal transport in mechanisms underlying AD due to pathological alterations in tau, the building block proteins of NFTs. This brief review summarizes insights into mechanisms whereby pathological alterations in tau impair axonal transport resulting in neurodegeneration and how these insights are being exploited now to develop novel therapeutic interventions for the treatment of AD.
Lee
Virginia M-Y
VM
The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and Institute on Aging, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. VMYLEE@mail.med.upenn.edu
Trojanowski
John Q
JQ
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D009410:Nerve Degeneration / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D016875:tau Proteins / Q000187:drug effects / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D016875:tau Proteins; D017239:Paclitaxel