Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventions

Abstract

Alzheimer's disease (AD) and cardiovascular disease (CVD) are syndromes of aging that share analogous lesions and risk factors, involving lipoproteins, oxidative damage and inflammation. Unlike in CVD, in AD, sensitive biomarkers are unknown, and high-risk groups are understudied. To identify potential prevention strategies in AD, we have focused on pre-clinical models (transgenic and amyloid infusion models), testing dietary/lifestyle factors strongly implicated in reducing risk in epidemiological studies. Initially, we reported the impact of non-steroidal anti-inflammatory drugs (NSAIDs), notably ibuprofen, which reduced amyloid accumulation, but suppressed few inflammatory markers and without reducing oxidative damage. Safety concerns with chronic NSAIDs led to a screen of alternative NSAIDs and identification of the phenolic anti-inflammatory/anti-oxidant compound curcumin, the yellow pigment in turmeric that we found targeted multiple AD pathogenic cascades. The dietary omega-3 fatty acid, docosahexaenoic acid (DHA), also limited amyloid, oxidative damage and synaptic and cognitive deficits in a transgenic mouse model. Both DHA and curcumin have favorable safety profiles, epidemiology and efficacy, and may exert general anti-aging benefits (anti-cancer and cardioprotective.)

Dietary n-3 PUFA deprivation alters expression of enzymes of the arachidonic and docosahexaenoic acid cascades in rat frontal cortex

“…Phospholipase A 2 activities Brain PLA 2 activities were measured in the cytosolic fraction as described in detail elsewhere, 14,36,39 with slight modifications to the extraction. For cPLA 2 activity, a portion of the cytoplasmic fraction was incubated in 100 mM 1-palmitoyl-2-arachidonoyl-snglycerol-3-phosphorylcholine (Avanti, Alabaster, AL, USA) and phosphatidylinositol 4,5-bisphosphate (97:3) containing approximately 100 000 cpm of 1-palmitoyl-2-[1-…”

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“…[15] Omega-3 fatty acid and phenolic anti-oxidant interventions are important dietary constituents which show antioxidant activity and anti-inflammatory responses. [16,17] Three important additions to the diet, i.e., capsaicin, curcumin (CM), and dietary n-3 fatty acids cause decrease in generation of reactive oxygen species in peritoneal macrophage[ Figure 1]. [17] Onions is used for arthritis treatment.…”

“…[16,17] Three important additions to the diet, i.e., capsaicin, curcumin (CM), and dietary n-3 fatty acids cause decrease in generation of reactive oxygen species in peritoneal macrophage[ Figure 1]. [17] Onions is used for arthritis treatment. [18] Ajoene, a natural product isolated from Allium shows anti-inflammatory properties.…”

Current and future uses of neuroimaging for cognitively impaired patients

“…[111][112][113][114] Some of these approaches might provide disease-modifying effects and slow progression of neurodegeneration. Although a neuroimaging biomarker for insoluble brain amyloid β might measure the biological effects of the intervention, a clinical trial design that would assess the progression of AD (eg, randomised withdrawal or randomised start design) would be necessary to prove diseasemodifying effects.…”