Correlation of pyroglutamate amyloid ? and ptau Ser202/Thr205 levels in Alzheimer's disease and related murine models.

ABSTRACT: Senile plaques frequently contain A?-pE(3), a N-terminally truncated A? species that is more closely linked to AD compared to other A? species. Tau protein is highly phosphorylated at several residues in AD, and specifically phosphorylation at Ser202/Thr205 is known to be increased in AD. Several studies suggest that formation of plaques and tau phosphorylation might be linked to each other. To evaluate if A?-pE(3) and ptau Ser202/Thr205 levels correlate in human and transgenic AD mouse models, we analyzed human cortical and hippocampal brain tissue of different Braak stages as well as murine brain tissue of two transgenic mouse models for levels of A?-pE(3) and ptau Ser202/Thr205 and correlated the data. Our results show that A?-pE(3) formation is increased at early Braak stages while ptau Ser202/Thr205 mostly increases at later stages. Further analyses revealed strongest correlations between the two pathologies in the temporal, frontal, cingulate, and occipital cortex, however correlation in the hippocampus was weaker. Evaluation of murine transgenic brain tissue demonstrated a slow but steady increase of A?-pE(3) from 6 to 12 months of age in the cortex and hippocampus of APPSL mice, and a very early and strong A?-pE(3) increase in 5xFAD mice. ptau Ser202/Thr205 levels increased at the age of 9 months in APPSL mice and at 6 months in 5xFAD mice. Our results show that A?-pE(3) and ptau Ser202/Thr205 levels strongly correlate in human as well as murine tissues, suggesting that tau phosphorylation might be amplified by A?-pE(3).

SUBMITTER: Neddens J 

PROVIDER: S-EPMC7347153 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature