Abstract
BackgroundAlzheimer disease (AD) is a neurodegenerative disorder for which there is no cure. We have investigated synaptic plasticity in area CA1 in a novel AD mouse model (APPPS1-21) which expresses the Swedish mutation of APP and the L166P mutation of human PS-1. This model shows initial plaque formation at 2 months in the neocortex and 4 months in the hippocampus and displays β−amyloid-associated pathologies and learning impairments.Methodology/Principal FindingsWe tested long-term potentiation (LTP) and short term potentiation (paired-pulse facilitation, PPF) of synaptic transmission in vivo in area CA1 of the hippocampus. There was no difference in LTP or PPF at 4–5 months of age in APPPS1-21 mice compared to littermate controls. At 6 months of age there was also no difference in LTP but APPPS1-21 mice showed slightly increased PPF (p<0.03). In 8 months old mice, LTP was greatly impaired in APPPS-21 animals (p<0.0001) while PPF was not changed. At 15 months of age, APPPS1-21 mice showed again impaired LTP compared to littermate controls (p<0.005), and PPF was also significantly reduced at 80 ms (p<0.005) and 160 ms (p<0.01) interstimulus interval. Immunohistological analysis showed only modest amyloid deposition in the hippocampus at 4 and 6 months with a robust increase up to 15 months of age.ConclusionsOur results suggest that increased formation and aggregation of beta amyloid with aging is responsible for the impaired LTP with aging in this mouse model, while the transient increase of PPF at 6 months of age is caused by some other mechanism.
Highlights
Alzheimer disease (AD) is a neurodegenerative disorder for which there is no cure
Our results suggest that increased formation and aggregation of beta amyloid with aging is responsible for the impaired long-term potentiation (LTP) with aging in this mouse model, while the transient increase of Paired-pulse facilitation (PPF) at 6 months of age is caused by some other mechanism
Spatial memory deficits in a plus maze task is apparent at the age of 8 months [3]. These findings suggest that the overproduction of bamyloid, the formation of plaques and the subsequent inflammation response is sufficient to produce a series of symptoms that are consistent with those observed in patients with AD
Summary
Alzheimer disease (AD) is a neurodegenerative disorder for which there is no cure. Two of the hallmarks are the accumulation of b-amyloid plaques and of tau tangles [1,2]. Spatial memory deficits in a plus maze task is apparent at the age of 8 months [3] These findings suggest that the overproduction of bamyloid, the formation of plaques and the subsequent inflammation response is sufficient to produce a series of symptoms that are consistent with those observed in patients with AD. We have investigated synaptic plasticity in area CA1 in a novel AD mouse model (APPPS1-21) which expresses the Swedish mutation of APP and the L166P mutation of human PS-1. This model shows initial plaque formation at 2 months in the neocortex and 4 months in the hippocampus and displays b2amyloid-associated pathologies and learning impairments
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