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.
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 .
Which disease the London mutation involved in?
Which disease the London mutation involved in ?
Alzheimer's Disease
Alzheimer's Disease AD