Immunohistochemical evidence for macroautophagy in neurones and endothelial cells in Alzheimer's disease.

AIM: To determine the pathological structures associated with macroautophagy in Alzheimer's disease (AD) and any relationship to disease progression.

METHODS

Immunohistochemistry using antibodies to beclin-1, Atg5 and Atg12, early macroautophagy markers and LC3, the mammalian homologue of the later macroautophagy marker Atg8, were localized in formalin-fixed, paraffin-embedded medial temporal lobe sections of AD cases at variable neuritic disease stages. Double immunofluorescence labelling was used to co-localize these macroautophagy markers with Abeta and phospho-tau (AT8) and correlations performed using Spearman rank tests.

RESULTS

Atg12 immunoreactivity in AD was either dispersed in the soma and dendrites or concentrated in tau-immunoreactive dystrophic neurites and some neurofibrillary tangles. Fewer Atg12-immunopositive neurones were observed with longer disease durations. Atg12-immunoreactive endothelial cells were found spatially associated with Abeta-positive plaques, with more Atg12-immunoreactive capillary endothelial cells with higher neuritic disease stage. These findings were confirmed by the other autophagy markers beclin-1, Atg5 and LC3.

CONCLUSION

The data confirm that macroautophagy occurs in neurones undergoing neuritic degeneration in AD, identified early macroautophagy markers in capillary endothelial cells in close proximity to Abeta plaques, and found that evidence for macroautophagy changes with disease progression.