Alzheimer’s disease is the most common form of dementia and is associated with a progressive age-dependent decline in cognitive ability. In this disease deposition of a peptide moelcule, amyloid β, forms amyloid plaques in those brain areas which are associated with learning and memory. This is a defining feature of brain pathology associated with Alzheimer’s disease. In collaboration with GlaxoSmithKline, Dr Fiona Le Beau, Dr Claudia Racca, Dr Mark Cunningham and Professor Miles Whittington have investigated the changes in the activity of the network of neurones in the cerebral cortex of a mouse model of Alzheimer’s disease. They used one mouse model, TAS10, that expresses large amounts of a mutated human amyloid precursor protein that results in abnormal deposition of amyloid β. Previous studies have shown that these TAS10 mice have learning deficits and develop amyloid plaques similar to those seen in human patients. In this study the group examined the oscillations in electrical activity which occur at a frequency of 30-80 Hz (so-called gamma oscillations) that are important for learning and memory and are known to be impaired in humans with Alzheimer’s disease. They found that at 8 months of age the TAS10 mice exhibited reduced oscillatory activity compared to the age-matched control mice. Importantly, this reduction occurred before formation of the amyloid plaques. When tested at 16 months of age the TAS10 mice showed no further deficits in oscillations but numerous amyloid deposits were now present in the hippocampus – a region important for learning where the recordings were made. These results are consistent with the current idea that decline in cognitive ability occurs early before plaque formation. Oscillatory activity was also reduced in the 16 month old control mice but the mechanisms underlying the reduction in the Alzheimer disease model appear to be distinct from those occurring in normal ageing. Understanding how this deficit occurs should aid the development of treatments aimed at restoring or maintaining cognitive function.
Impairment of hippocampal gamma (γ)-frequency oscillations in vitro in mice overexpressing human amyloid precursor protein (APP). Driver JE, Racca C, Cunningham MO, Towers SK, Davies CH, Whittington MA, LeBeau FEN (2007) European Journal of Neuroscience 26: 1280-1288 (PubMed abstract: http://www.ncbi.nlm.nih.gov/pubmed/17767505)
published on: 25th September 2007