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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 2010; 469(2):273-7NL

Abstract

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.

Authors+Show Affiliations

Graduate School of Biosphere Science, Hiroshima University, 1-7-1 Kagamiyama, Higashi-hiroshima 739-8521, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20025930

Citation

Hashimoto, Tetsuya, et al. "Age-dependent Increase in Lysosome-associated Membrane Protein 1 and Early-onset Behavioral Deficits in APPSL Transgenic Mouse Model of Alzheimer's Disease." Neuroscience Letters, vol. 469, no. 2, 2010, pp. 273-7.
Hashimoto T, Ogino K, Shin RW, et al. 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. 2010;469(2):273-7.
Hashimoto, T., Ogino, K., Shin, R. W., Kitamoto, T., Kikuchi, T., & Shimizu, N. (2010). Age-dependent increase in lysosome-associated membrane protein 1 and early-onset behavioral deficits in APPSL transgenic mouse model of Alzheimer's disease. Neuroscience Letters, 469(2), pp. 273-7. doi:10.1016/j.neulet.2009.12.015.
Hashimoto T, et al. 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. 2010 Jan 22;469(2):273-7. PubMed PMID: 20025930.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-dependent increase in lysosome-associated membrane protein 1 and early-onset behavioral deficits in APPSL transgenic mouse model of Alzheimer's disease. AU - Hashimoto,Tetsuya, AU - Ogino,Koichi, AU - Shin,Ryong-Woon, AU - Kitamoto,Tetsuyuki, AU - Kikuchi,Tetsuro, AU - Shimizu,Noriaki, Y1 - 2009/12/16/ PY - 2009/10/20/received PY - 2009/12/01/revised PY - 2009/12/09/accepted PY - 2009/12/23/entrez PY - 2009/12/23/pubmed PY - 2010/4/13/medline SP - 273 EP - 7 JF - Neuroscience letters JO - Neurosci. Lett. VL - 469 IS - 2 N2 - 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. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/20025930/Age_dependent_increase_in_lysosome_associated_membrane_protein_1_and_early_onset_behavioral_deficits_in_APPSL_transgenic_mouse_model_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(09)01585-7 DB - PRIME DP - Unbound Medicine ER -