Pathological Changes Induced by Amyloid-β in Alzheimer's Disease
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- TAKATA Kazuyuki
- Department of Neurobiology, Kyoto Pharmaceutical University
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- KITAMURA Yoshihisa
- Department of Neurobiology, Kyoto Pharmaceutical University
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- TANIGUCHI Takashi
- Department of Neurobiology, Kyoto Pharmaceutical University
Bibliographic Information
- Other Title
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- アミロイドβタンパク質依存性アルツハイマー病病変の研究
- アミロイド ベータ タンパクシツ イソンセイ アルツハイマービョウ ビョウヘン ノ ケンキュウ
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Description
The pathologic hallmarks of Alzheimer's disease (AD) include senile plaque, neurofibrillary tangles (NFTs), synaptic loss, and neurodegeneration. Senile plaque and NFTs are formed by accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, respectively. Progressive synaptic dysfunction and loss closely correlate with cognitive deficits in AD. Based on studies of the genes responsible for familial AD and temporal patterns of pathologic changes in AD brains, the Aβ accumulation is thought to be a primary event that influences other AD pathologies in the developmental cascade of AD. However, the details of Aβ effects on the other AD pathologies remain poorly understood. In this review, we provide an overview of the effects of Aβ in AD brains, especially focusing on synaptic dysfunction and microglia. We have recently found abnormal accumulation of a key molecule for actin assembly in NFTs of AD brains, and it was revealed that the accumulation requires not only tau pathology but also an Aβ burden in a study using transgenic mouse models of AD. Synaptic integrity is morphologically maintained by the precise regulation of actin assembly. Therefore, the results suggest the possibility that Aβ may promote NFT maturation and induce synaptic dysfunction through the disturbance of actin assembly. Thus Aβ seems to be a promoting factor in brain aging. On the other hand, we have studied microglial phagocytic ability for a compensatory pathologic reaction to Aβ accumulation. Further studies on the Aβ-dependent AD pathologies may contribute to determining novel mechanisms of AD development and new therapeutic targets in AD.<br>
Journal
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- YAKUGAKU ZASSHI
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YAKUGAKU ZASSHI 131 (1), 3-11, 2011-01-01
The Pharmaceutical Society of Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390282681104356864
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- NII Article ID
- 130000451519
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- NII Book ID
- AN00284903
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- ISSN
- 13475231
- 00316903
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- NDL BIB ID
- 10957971
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed