Aberrant ɑSMA expression reveals broad mossy fiber reorganization integrating with tangle and plaque formation and mitoenergetic alteration in the human hippocampus.

INTRODUCTION

Neural network and bioenergetic abnormalities occur with Alzheimer's disease (AD) pathogenesis.

METHODS

We explored mossy fiber (MF) and mitoenergetic alteration using ɑ-smooth muscle actin (ɑSMA) and cytochrome c oxidase (COX) immunolabeling in human hippocampus relative to tangle and plaque formation by referring to Braak (0-VI) and Thal (0-5) staging scores.

RESULTS

In the brain group with Braak/Thal 0/0 scores (control), ɑSMA labeling occurred in CA3 and dentate gyrus. In groups with 1a to IV/0 and II to VI/1 to 5 scores, ɑSMA labeling appeared in CA2 to subiculum, with increased density in these and the dentate subregions. ɑSMA-labeled MF terminals infiltrated into ghost tangles co-expressing amyloidogenic markers and coexisted among β-secreatse-1 labeled neurites and amyloid beta plaques. COX immunolabeling was increased in CA2 to subiculum in the groups with 1a to IV/0 to 1 compared to 0/0.

DISCUSSION: MF reorganization/dystrophy develops and integrates with tangle and plaque formation and mitoenergetic alteration in the human hippocampus.