ALZHEIMER鈥橲 disease may develop as a result of the brain trying to protect itself from over-excitation. A fine balance of excitatory and inhibitory signals is known to control nerve pathways involved in learning and memory, but it has been unclear how disruption of the balance could contribute to Alzheimer鈥檚.
Lennart Mucke from the University of California in San Francisco and his colleagues have now found evidence that the toxic beta-amyloid protein associated with Alzheimer鈥檚 disease can cause over-excitation of neurons in the brain鈥檚 learning centres. To protect neurons from what is often subtle damage, the brain rewires its circuitry to increase inhibitory signals.
A similar thing happens in epilepsy, where the brain cranks up inhibition to protect itself from the excitation of seizures. People with Alzheimer鈥檚 are also more likely to have seizures, and Mucke suggests that these, combined with the inhibitory rewiring, could make brain circuits unreliable and interfere with memory and learning. This may contribute to the symptoms of dementia (Neuron, ).
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The researchers are now testing whether anti-epileptic drugs could improve abnormal wiring and slow cognitive decline in the mouse form of Alzheimer鈥檚.
However, Clive Ballard of the Alzheimer鈥檚 Society in the UK says the model is probably only part of the story. For example, he says, the Alzheimer鈥檚 drug memantine targets overexcitation in the brain but has only moderate effects.
