INCREASED CATALASE ACTIVITY IN AGING ADULTS WITH DOWN SYNDROME: ASSOCIATIONS WITH AGE AND COGNITIVE DECLINE

Abstract

AbstractBackgroundThe aging process in Down syndrome (DS) is associated with a high prevalence of dementia, which is regarded as a variant form of early‐onset Alzheimer’s disease (AD). In addition to the central role played by amyloid pathology, DS‐dementia (DS‐D) may also be related to abnormal regulation of oxidative stress. The copper/zinc‐dependent superoxide dismutase (SOD1) gene is also located on chromosome 21, and studies have suggested an association of SOD1 overexpression with disrupted redox homeostasis. We hypothesize that such abnormalities may be further related to cognitive decline in DS.Method30 aging adults with DS were enrolled to the study, of whom 14 were cognitively stable (DS‐S) and 16 had evidence of cognitive decline (DS‐D). Two comparison groups were constituted with euploid volunteers, i.e., 30 age‐matched, cognitively healthy subjects (euploid controls, EU‐C); and 60 MCI and AD patients (EU‐MCI‐AD). We used an enzymatic assay to determine catalase activity.ResultAs compared to euploid controls, catalase activity was increased in DS irrespective of the presence of cognitive decline (p<0.004). This finding was also observed when the DS group was stratified according to the presence of cognitive decline (EU‐C vs. DS‐S, p<0.001; EU‐C vs. DS‐D, p<0.01). Catalase activity was also increased among cognitively stable DS as compared to MCI‐AD (DS‐S vs. EU‐MCI‐AD, p<0.027).When the DS group was stratified by age (18‐34y, 35‐49y, and ≥ 50y), catalase activity was found to be increased in younger and middle‐aged DS‐S as compared to EU‐C (18‐34y, p<0.01; 35‐49y, p<0.01) and in middle‐aged DS‐S as compared to SD‐D (35‐49y: p< 0.03).ConclusionOur preliminary findings suggest a systemic pro‐oxidant status in DS, evidenced by the increased catalase activity, presumably as a physiological compensation for redox imbalance due to the upregulation of SOD1 (data not shown). Furthermore, antioxidant defense functions decline with aging in the DS carrying. Thus, catalase could be a predictive biomarker candidate for AD.