Pathological Nuclear Hallmarks in Dentate Granule Cells of Alzheimer's Patients: A Biphasic Regulation of Neurogenesis.

The dentate gyrus (DG) of the human hippocampus is a complex and dynamic structure harboring mature and immature granular neurons in diverse proliferative states. While most mammals show persistent neurogenesis through adulthood, human neurogenesis is still under debate. We found nuclear alterations in granular cells in autopsied human brains, detected by immunohistochemistry.

Perinuclear Lamin A and Nucleoplasmic Lamin B2 Characterize Two Types of Hippocampal Neurons through Alzheimer's Disease Progression.

Background: Recent reports point to a nuclear origin of Alzheimer's disease (AD). Aged postmitotic neurons try to repair their damaged DNA by entering the cell cycle. This aberrant cell cycle re-entry involves chromatin modifications where nuclear Tau and the nuclear lamin are involved.

Aging dependent effect of nuclear tau.

Tau protein is characterized by a complex pattern of phosphorylation and is localized in the cytoplasm and nucleus in both neuronal and non-neuronal cells. Human AT100 nuclear tau, endowed by phosphorylation in Thr212/Ser214, was recently shown to decline in cornus ammonis 1 (CA1) and dentate gyrus (DG) in Alzheimer's disease (AD), but a defined function for this nuclear tau remains unclear. Here we show that AT100 progressively increases in the nuclei of neuronal and non-neuronal cells during aging, and decreases in the more severe AD stages, as recently shown, and in cancer cells (colorectal adenocarcinoma and breast cancer).