期刊
CURRENT ALZHEIMER RESEARCH
卷 17, 期 9, 页码 858-867出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567205017666201203125622
关键词
Alzheimer's disease; confocal microscopy; GFAP; hippocampus; human brain; huntingtin; immunohistochemistry; post-mortem
资金
- Swedish Research Council
- Hjarnfonden
- Margaretha af Ugglas foundation
- Swedish Alzheimer Foundation (Alzheimerfonden)
- foundation for Gamla Tjanarinnor
- Gun and Bertil Stohnes foundation
- Swedish Foundation for Dementia (Demensfonden)
Background: We have recently identified Huntingtin (Htt), the pathogenic protein in Huntington's disease, as a mediator of Alzheimer's disease (AD) pathology in an amyloid precursor protein (APP) knock-in mouse model of AD. That finding prompted us to examine if Htt is accumulated in the brains of AD patients and in which cell type Htt is present in the AD brain. Objective: To investigate whether location and levels of Htt are affected in hippocampus and frontal cortex in AD. Methods: Brains from AD patients (n=11) and controls (n=11) were stained for Htt using immunohistochemistry and signal intensity of Htt was quantified and localized in subregions and neurons. Confocal microscopy was used to characterize neuronal Htt localisation and its relationship with tau tangles and astrocytes. Results: Htt levels were increased in neuronal cells in the granular layer of the dentate gyrus, in CA1 and CA3 in hippocampus and in layer III of the frontal cortex. Htt was found in the soma, perinuclear space, thin neurites and nucleus of pyramidal neurons. Htt was present in neurons containing tau tangles but did not colocalize with astrocytes. Conclusion: Htt accumulates in pyramidal neuron-rich areas including hippocampal subregions associated with memory and frontal cortex layer III. The accumulation of Htt in AD shows distinct cellular and morphological patterns and is not present in astrocytes. Clearly, further research is warranted to elucidate the role of Htt as a mediator of AD pathology and the potential use of Htt as a target in future therapeutic strategies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据