Journal
BIOLOGICAL PSYCHIATRY
Volume 62, Issue 12, Pages 1405-1412Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2007.02.027
Keywords
Alzheimer's disease; glutamate; LTP; TMS
Categories
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available