Cortical plasticity in Alzheimer's disease in humans and rodents

Biol Psychiatry. 2007 Dec 15;62(12):1405-12. doi: 10.1016/j.biopsych.2007.02.027. Epub 2007 Jul 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Amyloid beta-Protein Precursor / genetics
  • Analysis of Variance
  • Animals
  • Calcium / metabolism
  • Case-Control Studies
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiopathology*
  • Disease Models, Animal*
  • Electromyography / methods
  • Evoked Potentials, Motor / physiology*
  • Evoked Potentials, Motor / radiation effects
  • Female
  • Humans
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Neuronal Plasticity / physiology*
  • Neuronal Plasticity / radiation effects
  • Presenilin-1 / genetics
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Time Factors
  • Transcranial Magnetic Stimulation / methods

Substances

  • Amyloid beta-Protein Precursor
  • Presenilin-1
  • Receptors, N-Methyl-D-Aspartate
  • Calcium