Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse models

Microglial P2X7receptor expression is accompanied by neuronal damage in the cerebral cortex of the APPswe/PS1dE9 mouse model of Alzheimer's disease

“…These findings suggest that P2X 7 R expression in microglia can be induced by soluble Aβ even very early in the course of AD pathogenesis. The ability of oligomeric Aβ to activate microglia provides crucial evidence that a soluble intermediate form of Aβ may cause oxidative damage prior to plaque formation in both humans and animal AD models (Pratico et al, 2001;Sonnen et al, 2008). Moreover, positron emission tomography studies of living AD patients, using the ligand PK11195, which specifically identifies activated microglia, have shown that microglial activation is evident even at early stages of the disease (Cagnin et al, 2001;Okello et al, 2009).…”

Biophenols of mints: Antioxidant, acetylcholinesterase, butyrylcholinesterase and histone deacetylase inhibition activities targeting Alzheimer’s disease treatment

“…An abundance of readily oxidizable polyunsaturated fatty acids and catalytic metal ions, along with inefficient antioxidant defense, make the brain a major site for oxidative damage (Butterfield et al, 2002). Excess formation of reactive oxygen and nitrogen species (RONS) has been repeatedly demonstrated in AD-affected brains in humans and in transgenic mouse models (Sonnen et al, 2008). In addition, decreased levels of acetylcholine in the brain areas related to memory and learning (the cholinergic hypothesis) and accumulation or disposal of amyloid b (Ab) (the amyloid hypothesis) are believed to be some of the main causes of AD (Korolev, 2014).…”

Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

“…Although the balance of published data suggests that antioxidants reduce the incidence and severity of dementia (3,4), the absence of a tool to follow brain antioxidant concentrations in living humans has hindered the development of an effectual intervention. The lack of ability to measure a pharmacologic effect is a documented hindrance to the development of antioxidant-based interventions against dementia (3).…”

“…Although the balance of published data suggests that antioxidants reduce the incidence and severity of dementia (3,4), the absence of a tool to follow brain antioxidant concentrations in living humans has hindered the development of an effectual intervention. The lack of ability to measure a pharmacologic effect is a documented hindrance to the development of antioxidant-based interventions against dementia (3). Given a recent finding that only when systemic antioxidants were depleted at baseline could a benefit of antioxidant-based treatment be realized (5), it follows that the inability to measure baseline antioxidant concentrations in the human brain has also been a hindrance to the development of interventions.…”