BetaAmyloid

Beta-amyloid, often abbreviated Aβ, is a peptide derived from the membrane protein called the amyloid precursor protein (APP). The most common forms found in humans are Aβ40 and Aβ42, with Aβ42 being more prone to aggregation. Aβ is produced when APP is sequentially cleaved by beta-secretase (BACE1) and gamma-secretase, releasing the soluble peptides outside the cell. APP is widely expressed, but the brain is particularly relevant for diseases linked to beta-amyloid.

In Alzheimer's disease, beta-amyloid can accumulate in the brain as extracellular plaques and as soluble oligomers. The oligomeric forms are thought to disrupt synaptic function and contribute to neuronal injury, while insoluble plaques are a characteristic histopathological feature of the disease. Beta-amyloid can also deposit in blood vessel walls, a condition known as cerebral amyloid angiopathy, which can contribute to vascular problems.

Genetics and risk factors influence beta-amyloid biology. Rare familial forms of Alzheimer's disease arise from mutations in APP, PSEN1, or PSEN2 that increase the production or aggregation tendency of Aβ, particularly Aβ42. The APOE ε4 allele is a major risk factor that decreases clearance of beta-amyloid from the brain and promotes aggregation.

Diagnosis and research approaches include imaging and fluid biomarkers. PET imaging with amyloid-specific tracers can show brain beta-amyloid deposition, and cerebrospinal fluid often shows reduced Aβ42 levels with concurrent markers of neurodegeneration. Therapeutic strategies have aimed to reduce production or promote clearance of beta-amyloid, but results have been mixed, and no universally effective disease-modifying therapy is established.