Loss of proteins regulating synaptic plasticity in normal aging of the human brain and in Alzheimer disease

Recent studies suggest that the cognitive impairment associated with normal aging is due to neuronal dysfunction rather than to loss of neurons or syn apses. To characterize this dysfunction, molecular indices of neuronal func tion were quantified in autopsy samples of cerebral cortex. During normal a ging, the most dramatic decline was found in levels of synaptic proteins in volved in structural plasticity (remodeling) of axons and dendrites. Alzhei mer disease, the most common cause of dementia in the elderly, was associat ed with an additional 81% decrease in levels of drebrin, a protein regulati ng postsynaptic plasticity. Disturbed mechanisms of plasticity may contribu te to cognitive dysfunction during aging and in Alzheimer disease.