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Oxidative balance in Alzheimer's disease: relationship to APOE, Braak tangle stage, and the concentrations of soluble and insoluble amyloid-β.
J Alzheimers Dis 2010; 22(4):1363-73JA

Abstract

Oxidative damage is greater in brain tissue from patients with Alzheimer's disease (AD) than age-matched controls. The timing of this damage in relation to other pathogenic processes in AD remains unclear. We have examined the relationship of lipid peroxidation (thiobarbituric acid-reactive substances; TBARS) and antioxidant capacity (Trolox-equivalent) to APOE status, Braak tangle stage, amyloid-β (Aβ) plaque load, and the concentration of soluble and insoluble forms of Aβ, post-synaptic and dendritic spine proteins PSD95 and drebrin, β-secretase and Aβ-degrading enzymes neprilysin (NEP), insulin-degrading enzyme (IDE), and angiotensin-converting enzyme (ACE), in frontal, temporal, and parietal cortex from AD and control brains. Antioxidant capacity was significantly elevated in AD and directly related to disease severity as indicated by Braak tangle stage and the amount of insoluble Aβ. APOE ε4 was associated with increased antioxidant capacity in AD but not controls. In contrast, apart from a reduction in TBARS in Braak stages III-IV in frontal cortex, this measure of oxidative damage did not change significantly with any indicator of disease severity. It was, however, higher in APOE ε4-positive than ε4-negative AD patients and correlated with β-secretase activity. Neither antioxidant capacity nor oxidative damage was related to the level of PSD95 or drebin or the activity of NEP, IDE, or ACE. Antioxidant capacity in AD is closely related to the level of insoluble Aβ and increases with pathological progression of the disease. Increased β-secretase activity associated with oxidative stress is likely to contribute to the accumulation of Aβ and this, in turn, to induce antioxidant capacity.

Authors+Show Affiliations

Dementia Research Group, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20930272

Citation

Tayler, Hannah, et al. "Oxidative Balance in Alzheimer's Disease: Relationship to APOE, Braak Tangle Stage, and the Concentrations of Soluble and Insoluble Amyloid-β." Journal of Alzheimer's Disease : JAD, vol. 22, no. 4, 2010, pp. 1363-73.
Tayler H, Fraser T, Miners JS, et al. Oxidative balance in Alzheimer's disease: relationship to APOE, Braak tangle stage, and the concentrations of soluble and insoluble amyloid-β. J Alzheimers Dis. 2010;22(4):1363-73.
Tayler, H., Fraser, T., Miners, J. S., Kehoe, P. G., & Love, S. (2010). Oxidative balance in Alzheimer's disease: relationship to APOE, Braak tangle stage, and the concentrations of soluble and insoluble amyloid-β. Journal of Alzheimer's Disease : JAD, 22(4), pp. 1363-73. doi:10.3233/JAD-2010-101368.
Tayler H, et al. Oxidative Balance in Alzheimer's Disease: Relationship to APOE, Braak Tangle Stage, and the Concentrations of Soluble and Insoluble Amyloid-β. J Alzheimers Dis. 2010;22(4):1363-73. PubMed PMID: 20930272.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidative balance in Alzheimer's disease: relationship to APOE, Braak tangle stage, and the concentrations of soluble and insoluble amyloid-β. AU - Tayler,Hannah, AU - Fraser,Thomas, AU - Miners,J Scott, AU - Kehoe,Patrick G, AU - Love,Seth, PY - 2010/10/9/entrez PY - 2010/10/12/pubmed PY - 2011/5/26/medline SP - 1363 EP - 73 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 22 IS - 4 N2 - Oxidative damage is greater in brain tissue from patients with Alzheimer's disease (AD) than age-matched controls. The timing of this damage in relation to other pathogenic processes in AD remains unclear. We have examined the relationship of lipid peroxidation (thiobarbituric acid-reactive substances; TBARS) and antioxidant capacity (Trolox-equivalent) to APOE status, Braak tangle stage, amyloid-β (Aβ) plaque load, and the concentration of soluble and insoluble forms of Aβ, post-synaptic and dendritic spine proteins PSD95 and drebrin, β-secretase and Aβ-degrading enzymes neprilysin (NEP), insulin-degrading enzyme (IDE), and angiotensin-converting enzyme (ACE), in frontal, temporal, and parietal cortex from AD and control brains. Antioxidant capacity was significantly elevated in AD and directly related to disease severity as indicated by Braak tangle stage and the amount of insoluble Aβ. APOE ε4 was associated with increased antioxidant capacity in AD but not controls. In contrast, apart from a reduction in TBARS in Braak stages III-IV in frontal cortex, this measure of oxidative damage did not change significantly with any indicator of disease severity. It was, however, higher in APOE ε4-positive than ε4-negative AD patients and correlated with β-secretase activity. Neither antioxidant capacity nor oxidative damage was related to the level of PSD95 or drebin or the activity of NEP, IDE, or ACE. Antioxidant capacity in AD is closely related to the level of insoluble Aβ and increases with pathological progression of the disease. Increased β-secretase activity associated with oxidative stress is likely to contribute to the accumulation of Aβ and this, in turn, to induce antioxidant capacity. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/20930272/Oxidative_balance_in_Alzheimer's_disease:_relationship_to_APOE_Braak_tangle_stage_and_the_concentrations_of_soluble_and_insoluble_amyloid_β_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2010-101368 DB - PRIME DP - Unbound Medicine ER -