To compare the presence of Lamin A, p-Tau and the heterochromatin marker H4K20me3 in hippocampal sections from control and AD brains.

It has been proposed that Alzheimer’s disease (AD) is an aging-associated laminopathy. In Drosophila melanogaster, structural Lamin B dysfunction mediates neurodegeneration linked to Tau protein. In human cells, Lamin A interacts with genome through lamin-associated domains (LADs) and regulates gene expression, but it's poorly expressed in neurons, and its participation in AD is unknown.

Paraffin sections obtained from control and AD brains at stages I-II, III-IV, and V-VI were processed for immunohistochemistry and immunofluorescence. The following nuclear, nucleolar, and heterochromatin specific markers were tested in the hippocampal CA1 and CA3 regions: p-Tau, Lamin A, B23 (nucleophosmin) and H4K20me3.

At initial AD stages(I-II), p-Tau leaves neuronal nuclei and accumulates in the cytoplasm leading to neurofibrillary tangles (AD stages III-VI). Simultaneously, a marked increase of Lamin A expression and H4K20me3 in LADs is observed in hippocampal pyramidal neurons.

Anomalous Lamin A expression and epigenetic changes that modify the heterochromatin structure are critical events at the beginning of neurodegeneration.