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Alzheimer's disease: β‐amyloid plaque formation in human brain
Author(s) -
Seeman Philip,
Seeman Neil
Publication year - 2011
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20957
Subject(s) - chemistry , amyloid (mycology) , peptide , fibril , membrane , p3 peptide , biochemistry , biophysics , microbiology and biotechnology , alzheimer's disease , amyloid precursor protein , disease , biology , medicine , pathology , inorganic chemistry
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. Synapse, 2011. © 2011 Wiley‐Liss, Inc.