Five point mutations within the amyloid beta-protein (Abeta) sequence of the APP gene are associated with hereditary diseases which are similar or identical to Alzheimer's disease and encode: the A21G (Flemish), E22G (Arctic), E22K (Italian), E22Q (Dutch) and the D23N (Iowa) amino acid substitutions.
The Dutch (E22Q) and Flemish (A21G) mutations in the betaAPP region of the amyloid precursor protein (APP) are associated with familial forms of Alzheimer dementia.
As the single substitution of Glu for Gln at position 22 of this peptide seems to be responsible for the manifestation of the more severe amyloidosis (Dutch-type), we decided to evaluate the aggregation characteristics of peptide analogs interchanging Glu and Gln residues at positions 22 and also 15 in the minor (12-24) (VHHQ(15)KLVFFAE(22)DV) fragment.
The Dutch (E22Q) and Flemish (A21G) mutations in the betaAPP region of the amyloid precursor protein (APP) are associated with familial forms of Alzheimer dementia.
Furthermore, a second peptide with a substitution similar to that in the Dutch-type hereditary amyloidosis mutation (Glu22 to Gln) was also found to be a substrate for transglutaminase.