Abstract
β amyloid peptide (Aβ) accumulation with aging is one of the main pathological features of Alzheimer Disease (AD). Aβ is produced from amyloid precursor protein (APP) by the action of β and γ secretase, it is degraded by some proteases such as neprilysin. Recently, β amyloid cleaving enzyme (BACE)was identified as β secretase and presenilin 1 is essential for the action of γ secretase. The alteration of activities of these substances with aging may induce to changes in turnover of Aβ and elevate the risk of AD. We therefore examined age-related changes of mRNA expressions in these substances. The hippocampus and cerebral cortex were dissected from young (4 weeks old)and aged (95 weeks old) rats and APP, BACE, presenilin 1 and neprilysin mRNA expressions in these tissues were measured by semi-quantitative RT-PCR method. GAPDH mRNA expressions were used for standardization of the template. In the hippocampus, BACE, presenilin 1 and neprilysin mRNA expressions were significantly reduced by aging, but there was no age difference in APP mRNA expression. In aged rats, the expression levels of BACE, presenilin 1 and neprilysin mRNA in the hippocampus were significantly lower than those in the cerebral cortex. Howevere, the mRNA expressions were examined didn't differ between the two brain regions in young rats. These results suggest that BACE, presenilin 1 and neprilysin mRNA expressions reduce only in the hippocampus with advancing age in rats. [Jpn J Physiol 54 Suppl:S215 (2004)]
