The neurochemical disturbances associated with AD have been studied for decades. As an explanation for the cognitive deficits of AD patients, the “cholinergic hypothesis” suggests that an acetylcholine deficiency is a critical component in the early stages of AD symptoms. The hypothesis has substantial support. Specifically, AD patients’ brains exhibit the following: A severe decrease in the activity of choline acetyltransferase (CAT), the enzyme that produces acetylcholine (ACh); significant degeneration of cholinergic neurons in the basalis of Meynert nucleus – a major source for cerebral cortex cholinergic innervation; and fewer presynaptic cholinergic receptors.

Other neurotransmitter abnormalities exist, although less rigorous evidence exists for their dyregulation.

A growing body of evidence suggests that disturbances in glutamatergic neurotransmission may underlie the neurobiology contributing to the cognitive deficits seen in patients with AD. In addition to its transmitter function, glutamate is a neurotoxin which has been implicated in the pathogenesis of a variety of neurodegenerative disorders, such as AD. Glutamate is a major excitatory neurotransmitter in the cerebral cortex and hippocampus that appears to have an important role in learning and memory. It has been suggested that the known risk factors for AD, such as age, heredity, head trauma, low education, and depression may all be related to glutamatergic dysfunction. As glutamatergic neurons in the cortex and hippocampus are damaged by AD, amyloid production in these regions may be enhanced by these deficits in glutamatergic neurotransmission.