- ɑSMA expression extends from CA3 and dentate gyrus to CA2 through subiculum, showing increased mossy fibre density across early to advanced Braak/Thal stages.
- ɑSMA-labelled mossy fibre terminals infiltrate ghost tangles co-expressing amyloidogenic markers and coexist with BACE1-positive neurites and amyloid-beta plaques.
- Cytochrome c oxidase immunolabelling increases in CA2 to subiculum in early Braak/Thal groups, indicating regional mitoenergetic alteration linked to mossy fibre reorganisation.
Alzheimers Dement. 2026 Aug;22(8):e71778. doi: 10.1002/alz.71778.
ABSTRACT
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.
PMID:42630074 | DOI:10.1002/alz.71778
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