Oxidative stress: A bridge between Down's syndrome and Alzheimer's disease

• Published in: Neurobiology of aging Vol. 28; no. 5; pp. 648 - 676
• Main Authors: Zana, Marianna, Janka, Zoltán, Kálmán, János
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2007
• Subjects: Alzheimer Disease - complications; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Amyloid beta-Protein Precursor - metabolism; Animals; Antioxidant therapy; Antioxidants - pharmacology; Antioxidants - therapeutic use; Biomarkers; Central nervous system; Down Syndrome - complications; Down Syndrome - drug therapy; Down Syndrome - metabolism; Down's syndrome; Humans; Internal Medicine; Neurology; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Periphery; Reactive Oxygen Species - metabolism; DHEA; APP; activator protein-1; advanced glycation end-product; HO; AP-1; Alzheimer's disease; γ-glutamyl-cysteine ethyl ester; nitric oxide; AD; CML; central nervous system; sister chromatid exchange; Biomarkers; glutathione peroxidase; NSAID; nuclear factor kappa B; senile plaque; CNS; alcohol dehydrogenase; heat shock protein; α-lipoic acid; single strand break; non-steroidal anti-inflammatory agent; glutamine synthase; cytoplasmic Cu 2+/Zn 2+ superoxide dismutase; GCEE; SP; CK; β-site amyloid precursor protein cleaving enzyme (β-secretase); RAGE; COX; BER; MCI; hydroxyl radical; LA; ALC; NER; oxidative stress; epigallocatechin gallate; ADH; 8-hydroxy-2′-deoxyguanosine; MDA; GPX; DS; Aβ; NF-κB; DSB; ferulic acid ethyl ester; cystathionine β-synthase; malondialdehyde; carbonyl reductase; NFT; catalase; N-acetyl- l-cysteine; heme oxygenase; 8-OH-dG; HSP; PUFA; receptor of advanced glycation end-product; EGCG; hydrogen peroxide; base excision repair; cyclooxygenase; TBARS; dehydroepiandrosterone; Periphery; H 2O 2; chromosome 21; CAT; cerebrospinal fluid; ROS; SOD-1; 8-hydroxyguanosine; FAEE; polyunsaturated fatty acid; amyloid beta protein; NO; dihydrolipoic acid; Antioxidant therapy; acetyl- l-carnitine; mtDNA; glutathione; NT; neurofibrillary tangle; CBR; Down's syndrome; amyloid precursor protein; CBS; CSF; reactive oxygen species; DHLA; OH; creatine kinase; GSH; AGE; Fe; homocysteine; N-epsilon-carboxymethyl-lysine; SSB; OS; double strand break; mitochondrial DNA; 8-OH-G; GS; 4-hydroxynonenal; Chr 21; NAC; thiobarbituric acid-reactive substance; SCE; iron; mild cognitive impairment; nitrotyrosine; HC; HNE; nucleotide excision repair; BACE; Central nervous system; Oxidative stress
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2006.03.008

Abstract Besides the genetic, biochemical and neuropathological analogies between Down's syndrome (DS) and Alzheimer's disease (AD), there is ample evidence of the involvement of oxidative stress (OS) in the pathogenesis of both disorders. The present paper reviews the publications on DS and AD in the past 10 years in light of the “gene dosage” and “two-hit” hypotheses, with regard to the alterations caused by OS in both the central nervous system and the periphery, and the main pipeline of antioxidant therapeutic strategies. OS occurs decades prior to the signature pathology and manifests as lipid, protein and DNA oxidation, and mitochondrial abnormalities. In clinical settings, the assessment of OS has traditionally been hampered by the use of assays that suffer from inherent problems related to specificity and/or sensitivity, which explains some of the conflicting results presented in this work. For DS, no scientifically proven diet or drug is yet available, and AD trials have not provided a satisfactory approach for the prevention of and therapy against OS, although most of them still need evidence-based confirmation. In the future, a balanced up-regulation of endogenous antioxidants, together with multiple exogenous antioxidant supplementation, may be expected to be one of the most promising treatment methods.