Secondary Chemical Bonding between Insoluble Calcium Oxalate and Carbonyl Oxygen Atoms of GLY and VAL Residues Triggers the Formation of Aβ Aggregates and Their Deposition in the Brain.

Despite intense efforts, the cause of Alzheimer's disease is still not fully understood. A chemical and biochemical perspective could shed light on this disorder. Secondary chemical bonding between calcium and carbonyl oxygen atoms of glycine and valine might give rise to aggregates in the brain, which may later result in cell senescence. The decrease of solubility caused by amino acid substitutions in specific risk factors compounds insolubility issue and likely triggers early-onset Alzheimer's disease. Occasionally the enhancement of hydrogen bonding by amino acid replacements can reinforce the aggregates. Therefore, secondary chemical bonding to cations can generate cellular stresses in patients with Alzheimer's disease in addition to other chemical and biochemical interactions such as salt bridge. The distinction between early-onset and late-onset Alzheimer's disease risk factors may lie in the total capacity of a protein or local potency of a protein fragment to bind calcium or/and oxalate as calcium oxalate is highly insoluble and stressful.