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

Tetsuya Hashimoto, Koichi Ogino, Ryong Woon Shin, Tetsuyuki Kitamoto, Tetsuro Kikuchi, Noriaki Shimizu

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Amyloid precursor protein (APP) is strongly related to the onset of Alzheimer's disease. It possesses cleavage sites for β- and γ-secretases, and the resulting cleaved products (amyloid-β 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-β and the ratio of amyloid-β 42/40 increased promptly in the brain during 6-16 months of age. Amyloid-β 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-β 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-β occurring during aging. Our findings coincided with the pathological hallmarks of Alzheimer's disease.

Original languageEnglish
Pages (from-to)273-277
Number of pages5
JournalNeuroscience Letters
Volume469
Issue number2
DOIs
Publication statusPublished - 2010 Jan 22

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Amyloid-β
  • LAMP-1
  • Memory impairment

ASJC Scopus subject areas

  • Neuroscience(all)

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