The intricacies of Alzheimer's disease
Early stages of Alzheimer's disease are characterised by a decline in learning ability, memory and attention. Recent studies showed that soluble amyloid beta (Abeta)–peptide oligomers cause degradation of the synapses in vitro. Now, it is important to connect in vitro observations with cognitive decline typical for Alzheimer's disease. Due to the difficulty of studying brain changes in living humans, the pathogenesis of Alzheimer's is researched in animal models. The project ABETACOGNITION performed research in vivo in mice. In order to find the interference of Abeta oligomers in cognitive ability, scientists studied memory, attention and response inhibition in mutant mice. To asses Abeta-oligomer–related neural changes, intracranial electroencephalography (EEG) and electromyography were recorded. In addition, a pharmacological study addressed the possibility to reverse the neural and cognitive changes by memantine (NMDA-receptor antagonist) and tiagabine (GABA-agonist). Behavioural experiments revealed that high concentrations of Abeta oligomers compromise the function of perirhinal and prefrontal cortexes. Injections of memantine into the perirhinal cortex reversed the object recognition impairment in mutant mice, while tiagabine had no effect and actually impaired object recognition in wild-type mice. The results show that pre-plaque Abeta oligomers occurring in the early stages of Alzheimer's disease participate in attention and memory deficits. The oligomers also cause neural changes, altering EEG in vivo. Both types of changes can be partially reversed by memantine, a drug used to treat Alzheimer's disease symptoms. The mere possibility of preventing or reversing the progression of Alzheimer's disease during the early stages is very exciting. It will help patients and lighten the burden of care and medical treatment they require.
