Alpha-, Beta-, and Gamma-Secretase, Amyloid Precursor Protein, and Tau Protein Genes in the Hippocampal CA3 Subfield in an Ischemic Model of Alzheimer’s Disease with Survival up to 2 Years

Abstract

Background: Understanding the phenomena underlying the non-selective susceptibility to ischemia of pyramidal neurons in the CA3 is important from the point of view of elucidating the mechanisms of memory loss and the development of dementia. Objective: The aim of the study was to investigate changes in genes expression of amyloid precursor protein, its cleaving enzymes and tau protein in CA3 post-ischemia with survival of 12–24 months. Methods: We used an ischemic model of Alzheimer’s disease to study the above genes using an RT-PCR protocol. Results: The expression of the amyloid precursor protein gene was above the control values at all times post-ischemia. The expression of the α -secretase gene also exceeded the control values post-ischemia. The expression of the β -secretase gene increased 12 and 24 months post-ischemia, and 18 months was below control values. Presenilin 1 and 2 genes expression was significantly elevated at all times post-ischemia. Also, tau protein gene expression was significantly elevated throughout the observation period, and peak gene expression was present 12 months post-ischemia. Conclusions: The study suggests that the genes studied are involved in the non-amyloidogenic processing of amyloid precursor protein. Additionally data indicate that brain ischemia with long-term survival causes damage and death of pyramidal neurons in the CA3 area of the hippocampus in a modified tau protein-dependent manner. Thus defining a new and important mechanism of pyramidal neuronal death in the CA3 area post-ischemia. In addition expression of tau protein gene modification after brain ischemia is useful in identifying ischemic mechanisms occurring in Alzheimer’s disease.

Trans- and Cis-Phosphorylated Tau Protein: New Pieces of the Puzzle in the Development of Neurofibrillary Tangles in Post-Ischemic Brain Neurodegeneration of the Alzheimer’s Disease-like Type

“…In this structure, the above genes were assessed in animals that lived 1, 1.5, and 2 years after ischemia. The changes virtually occurred at all times and were more intense ( Table 1 ) [ 35 ]. While changes in gene expression in the temporal cortex immediately occurred post ischemia and did not occur throughout survival and did not involve all genes ( Table 1 ) [ 36 , 37 ].…”

“…However, a significant increase in MAPT gene expression was observed 7–30 days after ischemia ( Table 1 ) [ 34 ]. In the CA3 area after ischemia with survival of 1, 1.5, and 2 years, overexpression of the MAPT gene was significant ( Table 1 ) [ 35 ].…”