Disproportionate Loss of Noradrenergic and Cholinergic Neurons as Cause of Depression in Alzheimer's Disease - A Hypothesis

Forty-two patients with neuropathologically confirmed Alzheimer's disease, who had been examined prospectively, had a significant decrease of neuron numbers in the locus coeruleus, substantia nigra, and basal nucleus of Meynert compared to 10 age-matched, non-demented controls. A subgroup of 12 demented patients with a history of depression had significantly lower neuron numbers in the locus coeruleus and slightly higher neuronal density in the basal nucleus of Meynert. We hypothesize that a noradrenergic/cholinergic imbalance may promote the development of depressive features in patients with Alzheimer's disease.