Low Phytanic Acid-Concentrated DHA Prevents Cognitive Deficit and Regulates Alzheimer Disease Mediators in an ApoE−/− Mice Experimental Model

Abstract

Alzheimer’s disease (AD) is the main cause of dementia and cognitive impairment. It has been associated with a significant diminution of omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) levels in the brain. Clinical trials with DHA as a treatment in neurological diseases have shown inconsistent results. Previously, we reported that the presence of phytanic acid (PhA) in standard DHA compositions could be blunting DHA’s beneficial effects. Therefore, we aimed to analyze the effects of a low PhA-concentrated DHA and a standard PhA-concentrated DHA in Apolipoprotein E knockout (ApoE−/−) mice. Behavioral tests and protein expression of pro-inflammatory, pro-oxidant, antioxidant factors, and AD-related mediators were evaluated. Low PhA-concentrated DHA decreased Aβ, ß-amyloid precursor protein (APP), p-tau, Ca2+/calmodulin-dependent protein kinase II (CAMKII), caspase 3, and catalase, and increased brain derived neurotrophic factor (BDNF) when compared to standard PhA-concentrated DHA. Low PhA-concentrated DHA decreased interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) protein expression in ApoE−/− mice when compared to standard PhA-concentrated DHA. No significant differences were found in p22phox, inducible nitric oxide synthase (iNOS), glutathione peroxidase (GPx), superoxide dismutase 1 (SOD-1), and tau protein expression. The positive actions of a low PhA-concentrated DHA were functionally reflected by improving the cognitive deficit in the AD experimental model. Therefore, reduction of PhA content in DHA compositions could highlight a novel pathway for the neurodegeneration processes related to AD.

Serum metabonomics analysis of quercetin against the toxicity induced by cadmium in rats

“…ω‐3 Polyunsaturated fatty acids have protective effects against central nervous system diseases, and high doses of DHA can reduce the risk of dementia among the elderly. [ 44 ]…”

Self-Reported Omega-3 Supplement Use Moderates the Association between Age and Exercising Cerebral Blood Flow Velocity in Older Adults

“…Regardless of the mechanism through which omega-3 supplement use stabilizes CBF, the consequent increased delivery of oxygen and nutrients to the brain could explain findings from other studies that show omega-3 fatty acids augment cognitive function and prevent cognitive decline [39][40][41][42]. For example, the connection between atherosclerosis and dementia has been well-established [43], and a meta-analysis of randomized controlled trials showed that omega-3 fatty acids significantly slowed the progression of atherosclerosis [44], suggesting that omega-3 fatty acids could potentially prevent cognitive decline through improvements in vascular health.…”