Alzheimer's Disease: β-Amyloid Plaque Formation in Human Brain

Although the precise cause of Alzheimer's disease is not known, the beta-amyloid peptide chains of 40-42 amino acids are suspected to contribute to the disease. The beta-amyloid precursor protein is found on many types of cell membranes, and the action of secretases (beta and gamma) on this precursor protein normally releases the b-amyloids at a high rate into the plasma and the cerebrospinal fluid. However, the concentrations of the beta-amyloids in the plasma and the spinal fluid vary considerably between laboratories. The beta-amyloids adsorb in the nanomolar concentration range to receptors on neuronal and glial cells. The beta-amyloids are internalized, become folded in the beta-folded or beta-pleated shape, and then stack on each other to form long fibrils and aggregates known as plaques. The beta-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 beta- and gamma-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 beta-amyloids. Synapse 65:1289-1297, 2011. (C) 2011 Wiley-Liss, Inc.