Alzheimer's mitochondrial face

Amyloid precursor protein targets to, and damages, mitochondria.

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Alzheimer's disease (AD), the most common form of dementia in the elderly, is characterized by a slow but progressive deterioration in cognitive performance. The main abnormal structures in the brains of affected people are neurofibrillary tangles and plaques. The latter consist of amyloid β peptides derived from amyloid precursor protein (APP), an integral transmembrane cell surface protein and a common constituent of normal healthy cells. In the April 14 Journal of Cell Biology, Hindupur Anandatheerthavarada and colleagues at the University of Pennsylvania, Philadelphia, US, report novel features of APP that could further our understanding of its role in AD (Journal of Cell Biology, 161:41-54, April 14, 2003).

Anandatheerthavarada et al. observed that the N-terminal domain of APP resembles that of some endoplasmic reticulum associated cell proteins, which use this signal in targeting mitochondria. They investigated intracellular APP localization using cultured human cortical neuronal (HCN-1A) cells and a transgenic mouse model ...

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