Neuritic plaque

Neuritic plaques, also known as senile plaques or amyloid plaques, are one of the hallmark pathological features of Alzheimer's disease (AD) and other forms of dementia. These plaques are extracellular deposits primarily composed of amyloid beta (Aβ) peptides in the brain tissue. The presence of neuritic plaques is a critical factor in the diagnosis of Alzheimer's disease and is considered a key target for therapeutic intervention.

Composition and Formation

Neuritic plaques consist mainly of dense cores of amyloid beta, a peptide that is derived from the larger amyloid precursor protein (APP) through sequential cleavage by beta-secretase and gamma-secretase. These enzymes cut APP into smaller fragments, including Aβ, which can then aggregate to form fibrils and eventually plaques. Surrounding the amyloid core, neuritic plaques also contain degenerating neuronal processes, including dendrites and axons, as well as activated microglia and astrocytes, which are indicative of an inflammatory response.

Pathology

The accumulation of amyloid beta and the formation of neuritic plaques in the brain are believed to disrupt cell-to-cell communication, activate immune responses leading to inflammation, and eventually cause the death of neurons. This neuronal loss is associated with the cognitive decline observed in Alzheimer's disease. The exact mechanism by which Aβ accumulation leads to neurodegeneration is still under investigation, but it is thought to involve a variety of cellular processes, including oxidative stress, mitochondrial dysfunction, and impaired calcium homeostasis.

Clinical Significance

The presence and distribution of neuritic plaques, along with neurofibrillary tangles (another hallmark of Alzheimer's disease), are used to determine the pathological stage of AD. Several imaging techniques, such as positron emission tomography (PET), have been developed to detect amyloid plaques in living patients, aiding in the early diagnosis and management of the disease.

Therapeutic Approaches

Current therapeutic strategies targeting neuritic plaques involve reducing the production of amyloid beta, preventing its aggregation, or facilitating its clearance from the brain. These approaches include the use of small molecule inhibitors of the secretases, immunotherapy with antibodies against amyloid beta, and promoting the activity of enzymes that degrade amyloid beta. However, the effectiveness of these treatments in altering the course of Alzheimer's disease remains a subject of ongoing research.

See Also

• Alzheimer's disease
• Amyloid beta
• Neurofibrillary tangles
• Dementia