Senile Plaques - Formation and Description

Formation and Description

Concentrated in the synapse of neurons is an Amyloid Precursor Protein (APP) that extends across the plasma membrane. A portion of this protein contains an Aβ peptide sequence. This region comprises part of the DNA segment spanning APP that codes for proteins.

In the formation of senile plaques, Aβ is cleaved from the amyloid precursor protein. Although three enzymes can process APP, only β- and γ-secretase are directly involved in the formation of senile plaques. β-secretase (BACE) is a protease enzyme that cleaves proteins and peptides. This protease cleaves APP to further expose the carboxyl terminal fragments of Aβ. After the bulk of APP is released by this process, γ-secretase cleaves the remaining carboxyl fragments on the transmembrane domain. The sequential actions of γ-secretase following BACE activity results in Aβ protein fragments (beta amyloid) that are released into the extracellular space. Eventually, the accumulation of beta amyloid outside of neuronal synapses forms an aggregate mass of plaque that pushes aside fine ramifications and connections of brain cells.

The formation of beta amyloid fragments is a normal occurrence in the human body. However, the accumulation of Aβ leading to the formation of plaque deposits is an unusual phenomenon. Although the cause of this abnormality is largely unknown, research has revealed certain species of beta amyloid that differ by a few amino acids in length that readily aggregate into plaques. These species are more pathogenic.

In an article written by Stone J. it was proposed that the formation of senile plaques is initiated by the bleeding from a cerebral capillary, which creates the conditions for the formation of an amyloid-rich plaque. This suggests that the spread of plaque formation is the capillary bed of the cerebral cortex, which sheds light on why plaque formation is age-related, since with age the capillary bed becomes fragile. Stone also suggested that a hemorrhage can create the condition for the formation of plaques, this explained why the features of the plaques consisted of being small and uniform in size; each plaque being the site of a capillary bleed.