The Role of Omega-6 Fatty Acid in Alzheimer’s Disease

Alzheimer’s disease (AD) is a major global health challenge, characterized by accumulation of amyloid plaques and neurofibrillary tangles. On account of this, PUFA have gained a major therapeutic strategy which plays role on Alzheimer’s disease by contributing effects as neuroprotective, anti-oxidant and anti-inflammatory properties. Among this, we review the dual effects of omega-6 fatty acid in relation to AD and performed the literature survey in databases like PubMed, google scholar and found that 30 articles were addressed the effect of omega-6 fatty acid in AD. Arachidonic Acid (ARA) and Linoleic Acid (LA) are central to the brain development and function. In that ARA contributes to the generation of pro-inflammatory mediators such as COX and LOX enzymes, which is responsible for the generation of pro-inflammatory cytokines, various in vivo and invitro studies have been reported that by inhibiting specific enzyme such as LOX and COX, the release of ARA can be stopped which prevent the generation of pro-inflammatory mediators. while, in some human studies have reported that circulating the higher ARA can produce the better cognitive outcomes and significantly reduce the dementia risk. In contrast to ARA, another acid such as LA have contributed to the anti-inflammatory properties and the reduced LA level may decrease the cognitive function and its isomer Conjugated linoleic acid (CLA) have also gained interesting therapeutic role as it has effect on the reduction of Aβ accumulation and tau phosphorylation, therefore it results in the uptake of anti-inflammatory cytokines and suppresses the inflammation. The derivative of LA such as Gamma Linoleic Acid (GLA) has inhibit the NF-kB which reduce the pro-inflammatory cytokines and also the MAPK signaling protect neurons from the amyloid toxicity. The balance of omega-3/omega-6 ratio (specifically AA: DHA) have been detected for the early AD biomarker. The therapeutic conclusion states that central target is not omega-6 fatty acids themselves but the metabolic pathway, future directions will focus on the metabolic pathway and which omega-6 will produce the anti-inflammatory effect and also the randomized controlled trials to establish the causal effects.