[27] Aβ is the main component of amyloid plaques, extracellular deposits found in the brains of people with Alzheimer's disease.

[citation needed] Research suggests that soluble oligomeric forms of the amyloid beta may be causative agents in the development of Alzheimer's disease.

[32] Several genetic, cell biology, biochemical and animal studies using experimental models support the concept that Aβ plays a central role in the development of Alzheimer's disease pathology.

[43] One study further correlated Aβ42 levels in the brain not only with onset of Alzheimer's disease, but also reduced cerebrospinal fluid pressure, suggesting that a build-up or inability to clear Aβ42 fragments may play a role into the pathology.

[44] The "amyloid hypothesis" — that the plaques are responsible for the pathology of Alzheimer's disease — is accepted by the majority of researchers, but is not conclusively established.

Much early development work on lead compounds has focused on this inhibition;[47][48][49] most are also reported to reduce neurotoxicity, but the toxic-oligomer theory suggests that prevention of oligomeric assembly is more important [50][51] For example, apomorphine was seen to significantly improve memory function through the increased successful completion of the Morris Water Maze.

[54] Aβ is formed after sequential cleavage of the amyloid precursor protein (APP), a transmembrane glycoprotein of undetermined function.

APP can be cleaved by the proteolytic enzymes α-, β- and γ-secretase; Aβ protein is generated by successive action of the β and γ secretases.

The γ secretase, which produces the C-terminal end of the Aβ peptide, cleaves within the transmembrane region of APP and can generate a number of isoforms of 30–51 amino acid residues in length.

[56] Autosomal-dominant mutations in APP cause hereditary early-onset Alzheimer's disease (familial AD, fAD).

Histochemical analysis of the APP V717I mutation has revealed extensive Aβ pathology throughout neuroaxis as well as widespread cerebral amyloid angiopathy (CAA).

[61] The gene for the amyloid precursor protein is located on chromosome 21, and accordingly people with Down syndrome have a very high incidence of Alzheimer's disease.

[62] Amyloid beta is commonly thought to be intrinsically unstructured, meaning that in solution it does not acquire a unique tertiary fold but rather populates a set of structures.

Antibodies that target Aβ and were tested in clinical trials included aducanumab, bapineuzumab, crenezumab, gantenerumab, lecanemab, and solanezumab.

[74][75] Atomic force microscopy, which can visualize nanoscale molecular surfaces, can be used to determine the aggregation state of amyloid beta in vitro.

[78] Recently, the formation of Aβ fibrils was resolved in different plaque-types in Alzheimer's disease, indicating that plaques transit different stages in their development.