Human butyrylcholinesterase knock-out equivalent: Potential to assess role in Alzheimer’s disease

Butyrylcholinesterase (BChE) is an enzyme which has been shown to be involved in the patho-genesis, treatment and prognosis of Alzheimer’s disease. In its current form, however, evidence is equivocal with all of the associations. Variant forms of the protein exist, where the enzymatic function is lost to varying degrees. We performed in silico evaluation of these variants. Bioinformatics and molecular modeling, based on data from ESTHER database and Protein Data Bank (RCSB), were used for in silico predictions of the structures of the silent variants that involve a single amino acid change. Variants with loss of enzyme activity were evaluated for structural changes near the active site and the thermody-namic stability of the variants was estimated. The results indicated that the loss of activity of the variants can, in most cases, be attributed to structural changes in the active site or to lower thermodynamic stability. Our results showed that the loss of enzyme activity may be due to changes in the active site, oligomerization or loss of structural stability. Individuals with loss of function mutation of BChE can be studied and followed up for their proneness or resistance to cognitive decline with aging.