Research
A study of long-term potentiation in transgenic mice over-expressing mutant forms of both amyloid precursor protein and presenilin-1
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* Corresponding author: Stephen M Fitzjohn stephen.fitzjohn@bris.ac.uk
1 MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, University Walk, Bristol, BS8 1TD, UK
2 The Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, UK
3 Merck Research Laboratories, 126 E. Lincoln Ave, Rahway, NJ 07065, USA
4 Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA
Molecular Brain 2010, 3:21 doi:10.1186/1756-6606-3-21
Published: 14 July 2010Abstract
Synaptic transmission and long-term potentiation (LTP) in the CA1 region of hippocampal slices have been studied during ageing of a double transgenic mouse strain relevant to early-onset familial Alzheimer's disease (AD). This strain, which over-expresses both the 695 amino acid isoform of human amyloid precursor protein (APP) with K670N and M671L mutations and presenilin 1 with the A246E mutation, has accelerated amyloidosis and plaque formation. There was a decrease in synaptic transmission in both wildtype and transgenic mice between 2 and 9 months of age. However, preparing slices from 14 month old animals in kynurenic acid (1 mM) counteracted this age-related deficit. Basal transmission and paired-pulse facilitation was similar between the two groups at all ages (2, 6, 9 and 14 months) tested. Similarly, at all ages LTP, induced either by theta burst stimulation or by multiple tetani, was normal. These data show that a prolonged, substantially elevated level of Aβ are not sufficient to cause deficits in the induction or expression of LTP in the CA1 hippocampal region.