Brain Region-Specific Differences in Amyloid-beta Plaque Composition in 5XFAD Mice

Senile plaques consisting of amyloid-beta (A beta) peptides are a major pathological hallmark of Alzheimer's disease (AD). A beta peptides are heterogeneous regarding the exact length of their amino- and carboxy-termini. A beta 1-40 and A beta 1-42 are often considered to represent canonical "full-length" A beta species. Using immunohistochemistry, we analyzed the distribution of A beta 1-x, A beta x-42 and A beta 4-x species in amyloid deposits in the subiculum, hippocampus and cortex in 5XFAD mice during aging. Overall plaque load increased in all three brain regions, with the subiculum being the area with the strongest relative plaque coverage. In the subiculum, but not in the other brain regions, the A beta 1-x load peaked at an age of five months and decreased thereafter. In contrast, the density of plaques positive for N-terminally truncated A beta 4-x species increased continuously over time. We hypothesize that ongoing plaque remodeling takes place, leading to a conversion of deposited A beta 1-x peptides into A beta 4-x peptides in brain regions with a high A beta plaque burden.