What is beta protein amyloid (A)?

Updated: May 09, 2019
  • Author: Robert O Holmes, Jr, DO; Chief Editor: Herbert S Diamond, MD  more...
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The amyloid beta precursor protein (AβPP), which is a transmembrane glycoprotein, is the precursor protein in beta protein amyloid (A). Three distinct clinical settings are as follows:

  • Alzheimer disease has a normal-sequence protein, except in some cases of familial Alzheimer disease, in which mutant beta protein is inherited in an autosomal dominant manner.

  • Down syndrome has a normal-sequence protein that forms amyloids in most patients by the fifth decade of life.

  • Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Dutch type, is inherited in an autosomal dominant manner. The beta protein contains a point mutation. These patients typically present with cerebral hemorrhage followed by dementia.

The accumulation of amyloid-β peptide (Aβ) in the brain both in the form of plaques in the cerebral cortex and in blood vessel as cerebral amyloid angiopathy (CAA) causes progressive cognitive decline. Researchers have used immunization strategies to neutralize amyloid fibrils before deposition. Experimental models and human clinical trials have shown that accumulation of Aβ plaques can be reversed by immunotherapy. Aβ immunization results in solubilization of plaque Aβ42 which, at least in part, exits the brain via the perivascular pathway, causing a transient increase in the severity of CAA. The extent to which these vascular alterations following Aβ immunization in Alzheimer disease are reflected in changes in cognitive function remains to be determined. [62]

Newer research has focused on finding a way to prevent the parent molecules from fragmenting and then aggregating to form toxic oligomers. Aβ peptide is known as a factor in the pathology of Alzheimer disease. Aβ aggregation is dependent on monomer concentration, nucleus formation, fibril elongation, and fibril fragmentation. Cellular, kinetic, and radiolabeling experiments have demonstrated that secondary nucleation occurs on the surface of only specific types of Aβ fibrils. The work focused on Aβ42, which could be a target molecule for future therapies to prevent nucleation events, oligomer formation rates, and neurotoxic effects. [63]

Other target fibrils with secondary amyloidogenic nucleation potential are also being investigated across large-scale comparative data sets. [64]

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