The presence of amyloid filled plaques is required for the definite diagnosis of AD. Amyloid plays a key role in the pathogenesis of AD, although it is not yet clear whether amyloid is the "cause" or the "consequence" of AD. The abnormal amyloid protein, beta amyloid, results from the cleavage product of amyloid precursor protein (APP). A gene for APP is located on Chromosome 21 (same chromosome associated with Down's syndrome). Amyloid is believed to adversely affect neuron function and survival. There are several theories as to how amyloid is toxic to the neurons.

Neurofibrillary tangles (NFTs), the second histologic hallmark of AD, are composed of paired helical filaments (PHFs). PHFs are composed of an abnormal tau protein, one of several microtubule associated proteins. The abnormal phosphorylation of tau results in an insoluble form of the protein which is believed to be responsible for the formation of PHFs and NFTs. The abnormal neurofilaments incorporated into the cell’s cytoskeleton are most likely involved in the impairment of cellular transport.

Localized inflammatory reactions in association with plaques and tangles have been identified. Acute phase reactants are present in plaques which may contribute to the disease process. Some studies have shown a decreased incidence of AD in patients with inflammatory diseases such as arthritis or those patients taking nonsteroidal antiinflammatory drugs (NSAIDs).