Lysophosphosphatidyl choline Docosahexaenoic acid (LPC-DHA)- Novel application for the Alzheimer disease and related dementia (ADRD)

Omega-3 fatty acids such as Docosahexaenoic acid (DHA) is exclusively concentrated in the brain and retina. It is very important for normal development for brain and retina function. Omega-3 fatty acid insufficiency contributes to several neurological disorders including Alzheimer’s disease and related dementia(ADRD),Parkinsons and Huntington’s disease. whereas high dietary intake of Omega-3 fatty acid is adversely associated with prevalence of ADRD. However, clinical trials using commercially available DHA rich oil failed to show improving memory in ADRD patients and animal models are very disappointing. The aim of this study is to identify the most efficient dietary carrier of DHA for enriching the brain DHA, and to determine whether such enhancement can prevent ADRD. We tested that enhancing brain DHA by dietary lysophosphaticylcholine DHA (LPC-DHA) prevents or postponements the development of ADRD in mouse models of 5XFAD mice. LPC-DHA was prepared and blended with rodent chow to yield the final DHA concentration of 0.35g/kg diet and fed to 5XFAD mice for 4 months, starting at the age of 1month.Control group was fed algal DHA oil containing DHA at the same dose in the form of TAG. Our results showed that LPC DHA significantly increased brain DHA (80-105%) in female 5XFAD mice as compared to algal DHA. LPC DHA also increases significantly brain DHA in female (40-50 fold) 5XFAD mice as compared to control and algal DHA fed mice. LPC-DHA altered locomotion and anxiety-like behavior. Interestingly it also improved memory-relevant behavior in female 5XFAD mice.The novel object test showed a significantly improved cognitive effect in LPC DHA fed mice as compared to control and algal DHA fed 5XFAD mice. This study could lead to a novel therapeutic approach for the prevention and treatment of ADRD.
 Funding :Alzheimer Association Research Grant(AARG-23-1151337)