Amyloid-beta (Aβ) pathology refers to the accumulation of Amyloid beta Aβ protein in the brain, which is a hallmark of Alzheimer's disease (AD). Aβ is a peptide that is produced when a larger protein called amyloid precursor protein (APP) is broken down. In healthy individuals, Aβ is cleared from the brain through various mechanisms, including degradation by enzymes and clearance by microglia and other immune cells. However, in AD, the clearance of Aβ is impaired, leading to its accumulation in the brain.
The accumulation of Aβ can trigger a cascade of events that lead to inflammation, oxidative stress, and neuronal damage, ultimately resulting in cognitive impairment and other symptoms of AD. The Aβ protein aggregates into fibrils that form beta-amyloid plaques, which are visible on brain imaging and are a defining feature of AD.
The presence of Aβ plaques in the brain is also associated with the formation of neurofibrillary tangles, which are made up of abnormal tau proteins. Tau proteins normally help to stabilize the structure of neurons, but in AD, they become abnormally modified and clump together, leading to the breakdown of the neuronal structure and function.
Aβ pathology is a major target of AD research, and there are currently several therapeutic approaches under investigation to target Aβ, including monoclonal antibodies that bind to and clear Aβ, vaccines that stimulate the immune system to clear Aβ, and small molecule drugs that inhibit Aβ production or promote its clearance. However, there is still much to learn about the complex role of Aβ in AD and the optimal strategies to target it for therapeutic benefit.
Cerebral amyloid angiopathy (CAA) is defined as the deposition of amyloid beta in the walls of the cortical and leptomeningeal vessels.