Background
The aim of this study was to determine whether neocortical long-term potentiation
(LTP) is deficient in patients with Alzheimer’s disease (AD) and in amyloid precursor
protein (APP)/presenilin-1 (PS1) mice, an AD animal model. We then ascertained whether
this deficit might be paralleled by functional abnormalities of N-methyl-D-aspartate
(NMDAR) glutamate receptors.
Methods
We studied neocortical LTP-like plasticity in 10 patients with mild-to-moderate AD
and 10 age-matched normal controls using paired associative stimulation (PAS). We
assessed neocortical (medial prefrontal cortex and primary motor cortex) and hippocampal
LTP in brain slices of symptomatic APP/PS1 mice. NMDAR composition and signaling as
well as synaptic calcium influx were determined in motor, prefrontal and hippocampal
cortices of APP/PS1 mice.
Results
Both AD patients and transgenic animals showed a deficit in NMDAR-dependent forms
of neocortical plasticity. Biochemical analysis showed impaired NMDAR function in
symptomatic APP/PS1 mice.
Conclusions
Neocortical plasticity is impaired in both patients with AD and APP/PS1 mice. The
results of our biochemical studies point to impaired NMDAR function as the most likely
cause for the neocortical plasticity deficit in AD.
Key Words
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Article info
Publication history
Published online: July 28, 2007
Accepted:
February 26,
2007
Received in revised form:
February 23,
2007
Received:
December 12,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
