There is approximately an 80% decrease in the large cholinergic neurons of the nucleus basalis of Meynart, and in parts of the reticular activating system, septum, and diagonal band. The extent of the cholinergic deficit correlates with the degree of cognitive impairment.

Serotonergic deficits are also typical in AD, and involve neurons in the dorsal raphe nuclei. This may explain sleep abnormalities and psychiatric changes. Noradrenergic deficits correlate with cell loss in the locus ceruleus and are often associated with earlier more aggressive disease. Noradrenergic deficits may correlate better with depression in AD than serotonergic deficits.

Since the ability to repair oxidative damage from free radicals seems to decline with aging, the free radical hypothesis of cell death may apply to AD. Free radicals are produced during metabolism of various biochemical substances. Some are necessary for normal organ function, but others, such as superoxide, may contribute to damage to enzymes, lipids, and nucleic acids. Antioxidants can prevent this damage from occurring. The use of antioxidants in the treatment of AD has been examined and will be discussed later in this module.