Amyloid plaques are accumulations of misfolded proteins that build up in the spaces between nerve cells. These protein deposits are recognized as a characteristic feature of several neurodegenerative diseases. Their presence in brain tissue is an area of research in understanding cognitive decline and related conditions.
The Formation of Amyloid Plaques
The creation of amyloid plaques begins with a protein called amyloid precursor protein (APP), which is found on the surface of neurons. Enzymes called secretases cut this larger protein into smaller pieces. Two of these enzymes, beta-secretase and gamma-secretase, sequentially cleave APP to produce fragments of amyloid-beta.
Not all amyloid-beta fragments are the same; they can vary in length. One particular variant, amyloid-beta 42 (Aβ42), is chemically “stickier” than other forms. This stickiness causes individual Aβ42 peptides to clump together, first forming small, soluble clusters called oligomers.
These oligomers continue to attract more amyloid-beta fragments, growing into larger, insoluble structures known as fibrils. Over time, these fibrils coalesce and deposit in the spaces between neurons, forming the dense, insoluble amyloid plaques. This entire process can occur over many years, often long before any external symptoms become apparent.
Impact on Brain Function
Once formed, amyloid plaques physically occupy the space between neurons, disrupting the connections known as synapses. These synapses are where nerve cells pass electrical and chemical signals to one another, forming the basis of all brain activity, including thought and memory. The presence of plaques weakens this signaling and the communication network within the brain.
The brain’s immune system also recognizes the plaques as harmful, triggering a sustained inflammatory response called neuroinflammation. Microglia, the primary immune cells of the central nervous system, become activated to clear the plaques. While this response is initially protective, its chronic activation contributes to a toxic environment.
This persistent state of inflammation, combined with the direct physical interference of the plaques, puts stress on the surrounding neurons. This environment can lead to synaptic dysfunction, damage to nerve cells, and neuronal death. The progressive loss of neurons and their connections is a direct contributor to the cognitive decline in associated diseases.
The Link to Alzheimer’s Disease
Amyloid plaques are a pathological hallmark of Alzheimer’s disease. For decades, the leading theory explaining their role has been the “amyloid cascade hypothesis.” This model proposes that the excessive accumulation of amyloid-beta peptides is the primary event that initiates a chain reaction leading to the other pathological changes seen in Alzheimer’s, including the formation of neurofibrillary tangles composed of tau protein.
According to this hypothesis, the build-up of amyloid plaques triggers downstream effects, including the abnormal modification of tau proteins inside neurons. These tau proteins, which normally help stabilize the internal structure of nerve cells, begin to misfold and clump together, forming tangles that disrupt cellular transport and lead to cell death. The combination of plaques between neurons and tangles within them drives the widespread neuronal loss that characterizes the disease.
The relationship is not entirely straightforward, as the number of amyloid plaques in the brain does not always correlate directly with the severity of cognitive symptoms. Some individuals may have significant plaque deposits without showing signs of dementia. This suggests that while plaques are a component of the disease process, other factors also influence the progression of Alzheimer’s.
Detection and Therapeutic Strategies
In living individuals, amyloid plaques are primarily detected through two advanced methods. Positron Emission Tomography (PET) scans can visualize plaques in the brain using radioactive tracers that bind to amyloid deposits. Another method involves analyzing cerebrospinal fluid (CSF), the fluid that surrounds the brain and spinal cord, which is collected via a lumbar puncture. Lower-than-normal levels of amyloid-beta in the CSF can indicate that the protein is accumulating in the brain as plaques instead of being cleared properly.
These detection methods helped develop therapeutic strategies targeting the plaques. A prominent approach involves anti-amyloid monoclonal antibodies, which are a class of drugs designed to target and help remove amyloid-beta from the brain. Medications like Lecanemab and Donanemab work by binding to different forms of amyloid, marking them for clearance by the body’s immune system.
These treatments have been shown to reduce the amount of plaque in the brain and can slow the rate of cognitive decline in the early stages of Alzheimer’s disease. They are not a cure and do not reverse existing damage. Research is also ongoing into lifestyle factors and other pharmacological interventions, such as those that modulate the secretase enzymes, to prevent plaque formation.