Decreased Blood Level of MFSD2a as a Potential Biomarker of Alzheimer’s Disease

Abstract

The protein Major Facilitator Superfamily Domain containing 2A (MFSD2a) was recently described as the primary carrier for docosahexaenoic acid (DHA) into the brain. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by lower DHA levels in blood lipids. The aim of this study was to investigate the expression of MFSD2a in the whole blood and brain as a potential biomarker of AD. Three groups were established: 38 healthy controls, 48 subjects with moderate AD (GDS4), and 47 with severe AD (GDS6). We analyzed postmortem brain samples from the hippocampus of 11 healthy controls and 11 severe AD patients. Fatty acid (FA) was determined in serum and brain by gas chromatography. Blood and brain MFSD2a protein expression was analyzed by Western blotting. We found a significant and progressive decline of MFSD2a levels in blood of AD patients (Control 0.83 ± 0.13, GDS4 0.72 ± 0.09, GDS6 0.48 ± 0.05*, p ˂ 0.01). We also corroborated a significant reduction of DHA and other n-3 long-chain polyunsaturated FA in serum of AD. No differences were found in MFSD2a expression or FA levels in brain of controls and AD subjects. MFSD2A carrier was analyzed in AD patients for the first time and the level of MFSD2a in the whole blood could be a potential biomarker of this disease.

Free Fatty Acids Are Associated with the Cognitive Functions in Stroke Survivors

“…More of the available evidence indicates the role of n6 to n3 PUFA ratio in the cognitive dysfunctions [ 44 , 45 ]. Other studies did not report any differences of this FA in AD patients compared to controls [ 43 ]. Observations presented by other authors differ from our results, but it should be emphasised that we investigated a specific group of stroke survivors and similar analyses have not been presented yet.…”

“…This FFA was found to be negatively associated with backwards repeating in Digit Span Test, which suggests its ambiguous role in predicting the working memory. In a limited number of studies available, no differences were identified in serum vaccinic acid level between AD patients and controls [ 43 ]. There are no available data regarding vaccinic acid and cognitive outcome in stroke patients.…”

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

“…A correlation between the primary fatty acid amide level in plasma and Aβ pathology, hippocampal volume, and cognitive score was also reported [ 310 ]. Instead, opposite trends were observed regarding the serum content of two saturated fatty acids (palmitic and myristic acids) and three unsaturated fatty acids (oleic, linolenic, and docosahexaenoic acids), with docosahexaenoic acid being the most significantly decreased in AD compared to controls [ 311 , 312 ].…”

The amplification of CNS damage in Alzheimer's disease due to SARS-CoV2 infection

“…The latter has also been associated with neuronal loss in Alzheimer's disease. The reduction of other proteins, including Src homology region 2 domain-containing phosphatase- 1 (SHIP1) [35] , [36] , BTB Domain And CNC Homolog 1 ( BACH1) [37] , [38] , BCL6 Transcription Repressor (BCL6) [39] , BCL10 Immune Signaling Adaptor (BCL10) [40] , [41] , and Major Facilitator Superfamily Domain Containing 2A (MFSD2A) [42] , [43] , have each been linked to progressive Alzheimer's disease. It has been shown in in vivo mouse models of COVID-19 that high circulating levels of spike protein can modulate some of these proteins in the brain and we have previously reported altered expression of NMDAR2, nNOS, SHIP1, and MFSD2A in the brains of people who died of COVID-19 who did not have a history of pre-existing dementia [11] .…”