Cortical plasticity in Alzheimer's disease in humans and rodents.
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.
Battaglia
Fortunato
F
City University of New York [CUNY] School of Medicine, Nathan Kline Institute, Orangeburg, New York, USA. fb@med.cuny.edu
Wang
Hoau-Yan
HY
Ghilardi
M Felice
MF
Gashi
Eleonora
E
Quartarone
Angelo
A
Friedman
Eitan
E
Nixon
Ralph A
RA
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004576:Electromyography / Q000379:methods; D019054:Evoked Potentials, Motor / Q000502:physiology* / Q000528:radiation effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009473:Neuronal Plasticity / Q000502:physiology* / Q000528:radiation effects; D053764:Presenilin-1 / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000379:methods
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium