Amyloid plaques

Amyloid_plaques

• Cerebral amyloid angiopathy with amyloid beta

• Neuritic Abeta plaques stained with NF-PAS

Amyloid Plaques

Amyloid plaques are extracellular deposits primarily composed of amyloid-beta (A_) peptides, which are associated with neurodegenerative diseases, most notably Alzheimer's disease. These plaques are a hallmark of Alzheimer's pathology and are found in the brains of affected individuals.

Structure and Composition

Amyloid plaques are primarily made up of amyloid-beta peptides, which are derived from the amyloid precursor protein (APP). The peptides aggregate to form insoluble fibrils that deposit in the extracellular space of the brain. These fibrils are organized into dense, spherical structures known as plaques. The core of the plaque is composed of a dense collection of fibrils, while the periphery may contain dystrophic neurites, activated microglia, and reactive astrocytes.

Formation

The formation of amyloid plaques begins with the cleavage of APP by enzymes known as secretases. The sequential action of beta-secretase and gamma-secretase results in the production of amyloid-beta peptides of varying lengths, with A_40 and A_42 being the most common. A_42 is more prone to aggregation and is considered more pathogenic. These peptides aggregate to form oligomers, protofibrils, and eventually mature fibrils that deposit as plaques.

Role in Alzheimer's Disease

Amyloid plaques are one of the two main pathological features of Alzheimer's disease, the other being neurofibrillary tangles composed of hyperphosphorylated tau protein. The "amyloid cascade hypothesis" suggests that the accumulation of amyloid-beta peptides and the formation of plaques are central to the pathogenesis of Alzheimer's disease. The presence of plaques is associated with synaptic dysfunction, neuroinflammation, and neuronal death, leading to the cognitive decline observed in patients.

Detection and Diagnosis

Amyloid plaques can be detected in the brain using imaging techniques such as positron emission tomography (PET) with amyloid-specific tracers. These imaging methods allow for the visualization of amyloid deposition in living patients, aiding in the diagnosis of Alzheimer's disease. Postmortem examination of brain tissue can also reveal the presence of plaques, confirming the diagnosis.

Therapeutic Approaches

Research into therapeutic approaches for Alzheimer's disease often targets the reduction of amyloid-beta production, aggregation, or plaque formation. Strategies include the development of secretase inhibitors, immunotherapy to promote clearance of amyloid-beta, and small molecules that prevent aggregation. Despite extensive research, effective treatments that significantly alter the course of the disease remain elusive.

Related Pages

• Alzheimer's disease
• Amyloid precursor protein
• Neurofibrillary tangles
• Tau protein
• Neurodegenerative diseases