Age-dependent increase in lysosome-associated membrane protein 1 and early-onset behavioral deficits in APPSL transgenic mouse model of Alzheimer's disease

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書誌事項

公開日
2010-01
資源種別
journal article
権利情報
  • https://www.elsevier.com/tdm/userlicense/1.0/
DOI
  • 10.1016/j.neulet.2009.12.015
公開者
Elsevier BV

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説明

Amyloid precursor protein (APP) is strongly related to the onset of Alzheimer's disease. It possesses cleavage sites for beta- and gamma-secretases, and the resulting cleaved products (amyloid-beta peptides) are capable of causing neurotoxicity. Such cleavage is promoted by the Swedish and London mutations (APPSwe/Lon) inside the APP gene. Here, we characterized APPSL transgenic mice (APPSL-Tg) to determine the effects of this mutation. We observed that both the amount of insoluble amyloid-beta and the ratio of amyloid-beta 42/40 increased promptly in the brain during 6-16 months of age. Amyloid-beta plaques were observed in whole brain sections at 12 months. In contrast, the spatial memory assessed by the Morris water maze task was already impaired at 3 months, which suggested that the APPSL-Tg mice may represent an early-onset model of familial Alzheimer's disease. Furthermore, the levels of LAMP-1, a marker protein of lysosome, increased in the brain at 28 months. Such LAMP-1 protein was detected around the amyloid-beta plaques at the hippocampal regions of the APPSL-Tg mice. Our results suggested that the increase in LAMP-1 was enhanced by the accumulation of amyloid-beta occurring during aging. Our findings coincided with the pathological hallmarks of Alzheimer's disease.

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