Figure 3.

Quantitation of amyloid-β N-terminus isomers. Scatter plots for the absolute quantitation of the N-terminus of Aβ peptides (A) total Aβ_1–15 and (B) total Aβ_4–15 in the three amyloid rich biochemical fractions of Na₂CO₃, urea-detergent and formic acid. Aβ peptides were compared between Alzheimer’s disease (n = 11) and control (n = 9) using mass spectrometry. The total levels of Aβ_1–15 and Aβ_4–15 are significantly elevated in Alzheimer’s disease tissue in all biochemical fractions. (C) Percentage ratio of most abundant Aβ_1–15 isomers and (D) Aβ_4–15 isomers in Alzheimer’s disease compared to control brains across different biochemical fractions. The unmodified Aβ_1–15 (native) is significantly decreased in all the biochemical fractions while doubly isomerized 1-iso, 7-iso-Asp Aβ_1–15 (10) diastereomer is significantly increased. The Aβ_4–15 isomer ratios demonstrated statistically significant changes in FA and Na₂CO₃ fractions. The pie charts summarize the pattern of distribution of isomerization of Aβ_1–15 and Aβ_4–15 in the different biochemical fractions. All the values are mean ± SD; significance in total Aβ_1–15 and Aβ_4–15 was determined by unpaired t-test with equal variance, while for the total amount of the Aβ_1–15 and Aβ_4–15 isomers and their normalized ratios, adjusted p values were calculated with ANOVA as described in the Materials and methods section. AD = Alzheimer’s disease; C = control, individual isomers of Aβ_1–15 and Aβ_4–15 are numbered according to Fig. 2.