Alzheimer's disease: β-amyloid plaque formation in human brain

Abstract

Although the precise cause of Alzheimer's disease is not known, the β-amyloid peptide chains of 40-42 amino acids are suspected to contribute to the disease. The β-amyloid precursor protein is found on many types of cell membranes, and the action of secretases (β and γ) on this precursor protein normally releases the β-amyloids at a high rate into the plasma and the cerebrospinal fluid. However, the concentrations of the β-amyloids in the plasma and the spinal fluid vary considerably between laboratories. The β-amyloids adsorb in the nanomolar concentration range to receptors on neuronal and glial cells. The β-amyloids are internalized, become folded in the β-folded or β-pleated shape, and then stack on each other to form long fibrils and aggregates known as plaques. The β-amyloids likely act as monomers, dimers, or multimers on cell membranes to interfere with neurotransmission and memory before the plaques build up. Treatment strategies include inhibitors of β- and γ-secretase, as well as drugs and physiological compounds to prevent aggregation of the amyloids. Several immune approaches and a cholesterol-lowering strategy are also being tested to remove the β-amyloids.