Frontiers in Clinical Drug Research - Alzheimer Disorders

Volume: 1

Indexed in: Scopus, EBSCO

Frontiers in Clinical Drug Research - Alzheimer Disorders is an e-Book series concerned with Alzheimer's disease (AD) that causes dementia, or loss of brain function. The disease affects the parts of ...
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Tau-Directed Therapies for Alzheimer’s Disease and Other Tauopathies

Pp. 147-182 (36)

Yasumasa Yoshiyama

Abstract

The rapid increase in size of the elderly population has resulted in a dramatic increase in the number of Alzheimer’s disease (AD) patients. To improve patients’ quality of life and reduce the economic and care burdens, the development of disease-modifying therapies directly related to the pathomechanism of AD is urgently needed. Based on the amyloid hypothesis, decreasing accumulation of Aβ in the brain is supposed to control downstream AD pathogenesis including formation of neurofibrillary tangles (NFTs) and neurodegeneration. However, the results of recent clinical trials in symptomatic AD patients aimed at Aβ removal, suppression of Aβ production or inhibition of Aβ aggregation have failed to demonstrate significant clinical efficacy. Moreover, active immunization with Aβ did not inhibit NFT formation, neurodegeneration or cognitive decline in AD patients even though it reduced Aβ burden in the brain. This suggests that Aβ-targeting therapies could not suppress tau-mediated neurodegeneration and it might autonomously progress, once it has been initiated. Therefore, the development of tau-directed therapies is an important and urgent issue for AD and related tauopathies. This chapter summarizes recent research progress in tau-directed therapies.

Keywords:

Alzheimer's disease, tauopathy, tau, neurodegeneration, progressive supranuclear palsy, Pick's disease, Frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, microtubule, GSK-3, neurofibrillary tangles, hyperphosphorylation, aggregation, axonal transport, dementia, microtubule biniding protein, truncation, fibrillization, misfolding, ubiquitination, lysosome, immunotherapy.

Affiliation:

Clinical Research Center, Department of Neurology, Chiba East National Hospital, Chiba, Chiba 260-8712, Japan.