Abstract
Based on the amyloid hypothesis, studies for AD therapy have been mostly focused on removing β-amyloid. Recent results of amyloid immunotherapy raised the question whether β-amyloid is sufficient target for AD therapy. Neurofibrillary tangles (NFTs), which contain hyperphosphorylated tau, are another pathological hallmark of AD. NFTs are observed in entorhinal cortex, limbic, and neocortex over the course of clinical progression. NFTs are associated with synapse and neuron loss, suggesting that the process of NFT formation is involved in brain dysfunction. During NFT formation, tau forms a variety of different aggregation species, including tau oligomers, granules, and fibrils. Analysis of different human tau-expressing mouse lines reveals that soluble hyperphosphorylated tau, which includes tau oligomer, is involved in synapse loss, whereas granular tau formation is involved in neuronal loss. Therefore, inhibition of tau aggregation and tau phosphorylation is expected to prevent synapse loss and neuron loss, and may slow or halt the progressive dementia in AD.
Keywords: Oligomer tau, granular tau, synapse loss, neuron loss.
Current Alzheimer Research
Title: TAU Aggregation is a Therapeutic Target for Alzheimers Disease
Volume: 7 Issue: 8
Author(s): A. Takashima
Affiliation:
Keywords: Oligomer tau, granular tau, synapse loss, neuron loss.
Abstract: Based on the amyloid hypothesis, studies for AD therapy have been mostly focused on removing β-amyloid. Recent results of amyloid immunotherapy raised the question whether β-amyloid is sufficient target for AD therapy. Neurofibrillary tangles (NFTs), which contain hyperphosphorylated tau, are another pathological hallmark of AD. NFTs are observed in entorhinal cortex, limbic, and neocortex over the course of clinical progression. NFTs are associated with synapse and neuron loss, suggesting that the process of NFT formation is involved in brain dysfunction. During NFT formation, tau forms a variety of different aggregation species, including tau oligomers, granules, and fibrils. Analysis of different human tau-expressing mouse lines reveals that soluble hyperphosphorylated tau, which includes tau oligomer, is involved in synapse loss, whereas granular tau formation is involved in neuronal loss. Therefore, inhibition of tau aggregation and tau phosphorylation is expected to prevent synapse loss and neuron loss, and may slow or halt the progressive dementia in AD.
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Cite this article as:
Takashima A., TAU Aggregation is a Therapeutic Target for Alzheimers Disease, Current Alzheimer Research 2010; 7 (8) . https://dx.doi.org/10.2174/156720510793611600
DOI https://dx.doi.org/10.2174/156720510793611600 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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