Nicotinic receptor subtypes in human brain related to aging and dementia

Neuronal nicotinic receptors are attracting increasing interest, beyond their role in relation to tobacco use, in the areas of human brain aging and disorders associated with dementia. Of the different receptor subtypes in the mammalian brain, many decline with normal aging in several different areas, including particularly cerebral cortex and hippocampus. There are further select subtype changes in the two most common forms of dementia in the elderly: Alzheimer's disease and dementia with Lewy bodies. The alpha4 subunit is most extensively reduced in the cortex in Alzheimer's disease, reflected in the loss of the high affinity binding site. There are also reductions in the low affinity binding site (alpha-bungarotoxin binding) in the thalamus in both disorders, which are likely to reflect the loss of the homomeric (most commonly alpha7) receptor subtype. Correlations exist between some of these receptor abnormalities and clinical and pathological features of the diseases. Targeting such receptors is a current therapeutic objective.