Alzheimer’s disease is a degenerative disorder of the brain that causes dementia. It is associated with loss of the cholinergic neurons that innervate the cerebral cortex. Impairment of cholinergic transmission is one possible explanation for the memory loss seen in this and other degenerative disorders. The precise mechanisms which cause Alzheimer's disease are still unknown. However, there is now clear evidence that certain factors predispose individuals to Alzheimer's disease. It is now clear that heredity plays an important role in the pathogenesis of Alzheimer's disease.

A larger percentage of patients suffer from a familial form of Alzheimer's disease associated with loci on chromosomes 14 or 1. The genes responsible for this form of Alzheimer's disease have recently been identified. They encode proteins with multiple transmembrane domains. The physiological function of these proteins is as yet unknown, although some research suggests that the mutations in these genes may increase the rate at which the amyloid protein is produced from its precursor.

Environmental risk factors may also play a major role. For example, there is evidence that head trauma could be a contributory factor. Although aluminum toxicity has not been ruled out as a contributory factor, there is as yet little strong evidence for a causal link.

The pathologic features of Alzheimer’s disease include cerebral atrophy with cell loss, particularly in the hippocampus, parahippocampus, and heteromodal association areas. The sensory and motor areas of the cortex are generally spared. The pathologic hallmarks are neurofibrillary tangles and senile plaques in the cortex, as well as granulovacuolar degeneration, amyloid deposition, and loss of cholinergic neurons in the nucleus basalis. There is also depletion of several neurotransmitters especially acetylcholine associated with Alzheimer’s disease.

Amyloid protein precursor (APP) is just that a precursor for the amyloid protein which is a polypeptide that is the single building block for amyloid plaques.

APP has features of an integral transmembrane cell surface protein and is a common component in the membrane of many normal healthy cells. The precise mechanism whereby APP is cleaved to produce the amyloid protein is the subject of a considerable amount of research activity today.

In addition to cleavage of APP to produce the amyloid protein, there is also some evidence that proteins like apolipoprotein E may also contribute to aggregation of amyloid protein to form amyloid plaques. Apolioprotein exists in three major forms, apoE2, apoE3, and apoE4. There has been some recent evidence showing that individuals with apoE4 have a slightly increased risk of getting Alzheimer’s disease between the ages of 65-75. It is estimated that 10% of all cases of Alzheimer’s disease is inherited, which suggests that the disease is caused by a mutation in a specific gene. There has not been research done yet to prove what specific gene mutations may be causing the disease. However it is possible there may be more than one involved, such as a gene encoding for apolipoprotein E, the APP gene, or genes known as presenilins.

There has been a number of studies and theories to determine what role amyloid plaques plays in the pathogenesis of Alzheimer’s disease. Some studies suggest that amyloid plaques are toxic to neurons, and that this results in the neurodegeneration seen in Alzheimer's disease. Numerous studies have shown that amyloid fibrils can disturb calcium homeostasis in cells. As calcium is important for release of neurotransmitters such as acetylcholine as well as helping to maintain homeostasis in the cell. Other studies suggest that changes in oxidative metabolism result from the build-up of amyloid fibrils. Such a hypothesis may help to explain why anti-oxidants such as Ginkgo biloba are beneficial. An inflammatory component to amyloid fibril toxicity may also play a role in the pathology of Alzheimer’s disease. Glial cells are commonly seen to invade neuritic plaques and may themselves be a source of APP or inflammatory cytokines which influence APP production by neurons. This may explain why anti-inflammatory drugs may be helpful.

There is still much research to be done to determine the exact role that the production of amyloid plaques plays in the pathogenesis of Alzheimer’s disease. The presence of plaques alone may not be enough to present with clinical symptoms of the disease, as many people at autopsy have been found to have plaques but did not have clinical Alzheimer’s disease. Other factors may also be involved. There is evidence to suggest that diffuse plaques may have to mature into so-called neuritic plaques prior to the onset of clinical symptoms. There is still great debate as to the significance amyloid plaques play in neurodegeneration. It is possible that the plaques are simply an end-stage of amyloid fibril build-up, or they may be a secondary feature of an underlying pathogenic mechanism. Regardless, it is very apparent that the overproduction of different forms of amyloid protein which aggregate in abundance is sufficient to cause Alzheimer’s disease. Currently all mutations in the presenilin and APP genes, which are pathogenic and which have been studied for their biochemical effects, have been shown to cause in increase in amyloid aggregation. It is highly unlikely that this amyloid aggregation is purely a coincidence among these mutations. This leads one to believe that amyloid aggregation is a necessary condition for disease pathogenesis.