Premium
Progressive age‐related development of Alzheimer‐like pathology in APP/PS1 mice
Author(s) -
Trinchese Fabrizio,
Liu Shumin,
Battaglia Fortunato,
Walter Sean,
Mathews Paul M.,
Arancio Ottavio
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20101
Subject(s) - long term potentiation , presenilin , neuroscience , genetically modified mouse , synaptic plasticity , hippocampus , amyloid precursor protein , psychology , alzheimer's disease , memory impairment , cognitive decline , amyloid (mycology) , transgene , medicine , cognition , disease , pathology , biology , dementia , biochemistry , receptor , gene
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‐β (Aβ) 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 Aβ 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. Aβ pathology across different ages did not correlate with synaptic and cognitive deficits, suggesting that Aβ 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. Ann Neurol 2004;55:801–814