Session Title: Alzheimer's Disease (AD) including Non-Cognitive Aspects
REMARKABLE EXPRESSION DIFFERENCES OF SOD1 AND SOD2 IN ALZHEIMER´S AND SWEDISH FAMILIAL ALZHEIMER´S BRAIN
E. Karelson1, K. Raud2, S. Kõks2, M. Zilmer1, N. Bogdanovic3
The primary defence of nerve cells against oxidative stress is provided by superoxide dismutases (SOD). In various models of Alzheimer's disease (AD), the activity and expression of SOD isoforms, cytosolic SOD1 and mitochondrial SOD2, reveal inconsistencies. In this study, the mRNA expression levels of SOD1 and SOD2 in four post-mortem neocortical regions (frontal, temporal, sensory postcentral, occipital primary cortex; FC, TC, SPCC, OPC) and hippocampus of aged-matched control persons and patients with AD and Swedish Familial AD (SFAD) were compared. The expression levels of SOD1 and SOD2 mRNA were detected by using TaqMan Assays Hs00166575_m1 (SOD1) and Hs00167309_m1 (SOD2). The results were analyzed by ΔCT method, were the level of target gene was normalized with the reference (HPRT-1) gene. We found that SOD1 expression is strikingly (3- to 8.5-fold) increased in SFAD brain regions and, to a lesser extent (2- to 2.5-fold), in sporadic AD brain regions, compared with control values. The associative FC of SFAD brain displayed the largest (8.5-fold) increase in the expression. The SFAD- and AD-induced 2- to 5.5-fold increase of SOD2 expression was confined to TC, FC and SPCC, being largest in SFAD FC. We suggest that differential over-expression of SOD isoforms in SFAD and AD brain serves as an attempt to counteract the region-specific oxidant-antioxidant imbalance. The study could be helpful in determining the antioxidant defence of brain regions in sporadic and familial AD patients and in predicting the patient's response to therapeutic antioxidant intervention.The study was funded by Estonian Scientific Foundation (Grant No. 6574).