| First Author | Hashimoto T | Year | 2010 |
| Journal | Neurosci Lett | Volume | 469 |
| Issue | 2 | Pages | 273-7 |
| PubMed ID | 20025930 | Mgi Jnum | J:156882 |
| Mgi Id | MGI:4421621 | Doi | 10.1016/j.neulet.2009.12.015 |
| Citation | Hashimoto T, et al. (2010) Age-dependent increase in lysosome-associated membrane protein 1 and early-onset behavioral deficits in APPSL transgenic mouse model of Alzheimer's disease. Neurosci Lett 469(2):273-7 |
| abstractText | 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. |
