Amyloid Beta 42/40

Amyloid beta (Aβ) peptides are small protein fragments produced when a larger protein, called amyloid precursor protein (APP), is broken down in the body. Among these peptides, Aβ40 and Aβ42 are the most important. Aβ40 makes up about 90% of amyloid beta produced, while Aβ42 is less common but more prone to clump together, forming the sticky plaques found in the brains of people with Alzheimer’s disease (AD).

Aβ42 tends to start forming plaques earlier than Aβ40. Although both proteins are involved in the disease process, Aβ42 is more harmful because it is more likely to form insoluble deposits that disrupt normal brain function. These plaques are one of the hallmarks of Alzheimer’s disease. Interestingly, while Aβ40 is also involved, it seems to behave differently: in Alzheimer’s disease, Aβ40 levels might decrease moderately, while Aβ42 levels drop more sharply. This difference is why the ratio of Aβ42 to Aβ40 is such a powerful marker — a lower ratio points strongly toward Alzheimer’s, even when other tests might still look normal.

Testing for the Aβ42/Aβ40 ratio has become a crucial tool for detecting Alzheimer’s early. It often matches what is seen in brain imaging scans and can catch disease processes years before symptoms like memory loss appear. A low Aβ42/Aβ40 ratio can also help distinguish Alzheimer’s from other types of dementia, such as dementia with Lewy bodies (DLB), because the pattern of changes differs between these diseases.

In the body, Aβ42 is usually cleared through several pathways: it can form fibrils (long protein chains that clump together), be flushed into cerebrospinal fluid, or be broken down by specialized enzymes. However, in Alzheimer’s disease, there seems to be an unusual increase in how quickly the body removes soluble (non-clumped) Aβ42, possibly pushing more Aβ42 into harmful aggregates inside brain cells. Maintaining the right balance between production, clearance, and aggregation of Aβ42 is critical for brain health.

Structurally, Aβ42 is slightly longer than Aβ40, and that small difference makes it much more likely to form toxic clumps. In laboratory studies, these two forms of amyloid behave differently when forming fibrils and interacting with brain cells. Changes in the structure or production of these proteins, often due to genetic mutations like the V717F mutation in APP, can dramatically affect the ratio of Aβ42 to Aβ40.

In short, Aβ40 and Aβ42 are important clues to what is happening inside the brain long before Alzheimer’s disease causes obvious symptoms. Watching their levels, especially the ratio between them, offers an important window into brain health and opens up earlier possibilities for intervention.