Fibrils of amyloid peptide molecules stack together to form a long, ribbon-like peptide arrays that aggregate to form the characteristic Alzheimer plaques. The formation of these pathological peptides is partially understood. It appears that only the aggregated fibrillar forms of the beta-amyloid peptide are toxic. When these fibrils contact neurons, they open channels in the cell that allow large amounts of calcium to enter. Elderly brain cells are particularly vulnerable to this because they have diminished ability to use the tactics cells normally use to get rid of excess calcium.
Calcium helps cells do many things, including carry nerve signals.
Neurons normally are very careful about the amount of calcium they allow in because they use minute changes in levels of internal calcium to interpret messages from other neurons. Too much calcium inside cells leads to cell death. To do this, the researchers selected from a combinatorial library a series of peptides with various interesting properties. Peptides are natural or synthetic compounds of two or more linked amino acids, the most basic building blocks of life. Ingram and his research team created 30 small peptides, each between five and eight amino acids long, and tested them with lab-cultured human nerve cells.