Macroscopically, the brain appears normal in early AD. However, there is substantial atrophy in advanced disease. Areas of atrophy include the frontal, temporal and parietal lobes of the neocortex. Cerebral convolutions are narrowed, sulci are widened and the ventricles are symmetrically enlarged. There is a 60% loss in cortical neurons, loss of dendrites, neuronal atrophy and granulovacuolar degeneration.

In 1981, Whitehouse et al identified the anatomic region of the brain consistent with neurochemical deficiency and clinical derangements seen in AD. This region, the nucleus basalis of Meynart, revealed cell loss and cytopathological abnormalities which the authors attributed to the cognitive and behavioral disturbances seen in AD.

In primates, the nucleus basalis receives input from a variety of sources, including the amygdala, the hypothalamus and other midbrain and brainstem nuclei. The nucleus basalis sends projections to several brainstem nuclei, to the hippocampus and frontal and parietal lobes. Acetylcholine is a major transmitter in the nucleus basalis and these neurons are rich in acetylcholinesterase, the enzyme which degrades acetylcholine.