Tags

Type your tag names separated by a space and hit enter

Progressive age-related development of Alzheimer-like pathology in APP/PS1 mice.
Ann Neurol 2004; 55(6):801-14AN

Abstract

Increasing evidence points to synaptic plasticity impairment as one of the first events in Alzheimer's disease (AD). However, studies on synaptic dysfunction in different transgenic AD models that overexpress familial AD mutant forms of amyloid precursor protein (APP) and/or presenilin (PS) have provided conflicting results. Both long-term potentiation (LTP) and basal synaptic transmission (BST) have been found to be both unchanged and altered in different models and under differing experimental conditions. Because of their more robust amyloid-beta (Abeta) deposition, double transgenic mice currently are used by several laboratories as an AD model. Here, we report that mice overexpressing APP (K670N:M671L) together with PS1 (M146L) have abnormal LTP as early as 3 months of age. Interestingly, reduced LTP paralleled plaque appearance and increased Abeta levels and abnormal short-term memory (working memory). BST and long-term memory (reference memory) are impaired only later (approximately 6 months) as amyloid burden increases. Abeta pathology across different ages did not correlate with synaptic and cognitive deficits, suggesting that Abeta levels are not a marker of memory decline. In contrast, progression of LTP impairment correlated with the deterioration of working memory, suggesting that percentage of potentiation might be an indicator of the cognitive decline and disease progression in the APP/PS1 mice.

Authors+Show Affiliations

Department of Psychiatry, New York University School of Medicine, New York, NY, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15174014

Citation

Trinchese, Fabrizio, et al. "Progressive Age-related Development of Alzheimer-like Pathology in APP/PS1 Mice." Annals of Neurology, vol. 55, no. 6, 2004, pp. 801-14.
Trinchese F, Liu S, Battaglia F, et al. Progressive age-related development of Alzheimer-like pathology in APP/PS1 mice. Ann Neurol. 2004;55(6):801-14.
Trinchese, F., Liu, S., Battaglia, F., Walter, S., Mathews, P. M., & Arancio, O. (2004). Progressive age-related development of Alzheimer-like pathology in APP/PS1 mice. Annals of Neurology, 55(6), pp. 801-14.
Trinchese F, et al. Progressive Age-related Development of Alzheimer-like Pathology in APP/PS1 Mice. Ann Neurol. 2004;55(6):801-14. PubMed PMID: 15174014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progressive age-related development of Alzheimer-like pathology in APP/PS1 mice. AU - Trinchese,Fabrizio, AU - Liu,Shumin, AU - Battaglia,Fortunato, AU - Walter,Sean, AU - Mathews,Paul M, AU - Arancio,Ottavio, PY - 2004/6/3/pubmed PY - 2004/7/13/medline PY - 2004/6/3/entrez SP - 801 EP - 14 JF - Annals of neurology JO - Ann. Neurol. VL - 55 IS - 6 N2 - Increasing evidence points to synaptic plasticity impairment as one of the first events in Alzheimer's disease (AD). However, studies on synaptic dysfunction in different transgenic AD models that overexpress familial AD mutant forms of amyloid precursor protein (APP) and/or presenilin (PS) have provided conflicting results. Both long-term potentiation (LTP) and basal synaptic transmission (BST) have been found to be both unchanged and altered in different models and under differing experimental conditions. Because of their more robust amyloid-beta (Abeta) deposition, double transgenic mice currently are used by several laboratories as an AD model. Here, we report that mice overexpressing APP (K670N:M671L) together with PS1 (M146L) have abnormal LTP as early as 3 months of age. Interestingly, reduced LTP paralleled plaque appearance and increased Abeta levels and abnormal short-term memory (working memory). BST and long-term memory (reference memory) are impaired only later (approximately 6 months) as amyloid burden increases. Abeta pathology across different ages did not correlate with synaptic and cognitive deficits, suggesting that Abeta levels are not a marker of memory decline. In contrast, progression of LTP impairment correlated with the deterioration of working memory, suggesting that percentage of potentiation might be an indicator of the cognitive decline and disease progression in the APP/PS1 mice. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/15174014/Progressive_age_related_development_of_Alzheimer_like_pathology_in_APP/PS1_mice_ L2 - https://doi.org/10.1002/ana.20101 DB - PRIME DP - Unbound Medicine ER -