학술논문

Protein kinase C delta accumulates in neurofibrillary tangles in Alzheimer’s disease
Document Type
Journal Article
Source
Biwako Journal of Rehabilitation and Health Sciences. 2022, 1:29
Subject
Alzheimer’s disease
human brain
immunohistochemistry
neurofibrillary tangle
protein kinase C delta
Language
English
ISSN
2758-1780
2758-1799
Abstract
The protein kinase C (PKC) family is associated with tau pathology in Alzheimer’s disease (AD). PKCδ, a novel PKC isoform, has universal, rather than cell-type-specific, roles in the human brain and may be critical for cellular functions, such as control of growth, differentiation, and apoptosis. However, little information is available regarding the localization and function of PKCδ in the AD brain. In this study, we investigated PKCδ localization in postmortem human brain tissues from elderly individuals (controls) and patients with AD using immunohistochemistry. In control brains, punctate staining of PKCδ was observed in the cytoplasm, nuclei of granules and pyramidal neurons in the hippocampus. In AD brains, PKCδ expression in neuronal cell bodies was lower than that in controls. Numerous neurofibrillary tangles (NFTs) and degenerative neurites within senile plaques were strongly immunopositive for PKCδ in the AD hippocampus. Residual neurons were weakly positive in the AD hippocampi compared to the control, and many intracellular NFTs were strongly positive for PKCδ in the CA1 subfield and the subiculum. Immunoelectron microscopy of the AD hippocampus showed that PKCδ was localized in the paired helical filaments of NFTs, nuclei, small vesicles, and lysosomes. Double immunostaining showed that PKCδ was extensively colocalized with glycogen synthase kinase 3β (GSK3β), which is involved in tau pathology. These results suggest that PKCδ is localized to paired helical filaments in intracellular NFTs in the AD brain and plays an important role in tau pathology.