Amyloid plaque

Amyloid Plaque

Amyloid plaques are extracellular deposits primarily composed of amyloid-beta (Aβ) 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.

Formation

Amyloid plaques form when amyloid-beta peptides aggregate into insoluble fibrils. These peptides are derived from the amyloid precursor protein (APP), which is cleaved by enzymes known as secretases. The cleavage by beta-secretase and gamma-secretase results in the production of amyloid-beta peptides of varying lengths, with Aβ42 being particularly prone to aggregation.

Structure

The structure of amyloid plaques consists of dense cores of fibrillar amyloid-beta surrounded by dystrophic neurites, activated microglia, and reactive astrocytes. The fibrils are arranged in a beta-sheet conformation, which contributes to their stability and resistance to proteolytic degradation.

Pathophysiology

The accumulation of amyloid plaques in the brain is believed to disrupt cell-to-cell communication and activate immune responses, leading to inflammation and neuronal damage. This process is thought to contribute to the cognitive decline observed in Alzheimer's disease.

Diagnosis

Amyloid plaques can be detected in vivo using positron emission tomography (PET) imaging with amyloid-specific tracers. Post-mortem analysis of brain tissue can also reveal the presence of plaques through histological staining techniques such as Congo red or thioflavin S.

Therapeutic Approaches

Research into therapeutic approaches for reducing amyloid plaque burden includes the development of drugs that inhibit the production of amyloid-beta, promote its clearance, or prevent its aggregation. Immunotherapy, using antibodies that target amyloid-beta, is one area of active investigation.

Also see

• Alzheimer's disease
• Neurofibrillary tangles
• Amyloid precursor protein
• Beta-secretase
• Gamma-secretase