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.

Highlights

  • Alzheimer’s disease (AD) is a progressive, irreversible, neurodegenerative disorder and one of the most common causes of dementia in old age

  • We aimed to study whether Major Facilitator Superfamily Domain containing 2A (MFSD2a) level is altered in the blood of AD patients, which are easy-to-obtain samples by noninvasive procedures, on different stages of the disease as a potential biomarker of AD

  • We reported for the first time a continuous decline of MFSD2a protein level in blood of patienWtse rwepitohrtdeidffeforerntht egrfiardstestimofeAaDco, nthtienudoifufserdeenccleinseboefinMgFsStDat2isatipcraolltyeinsiglenvifeilcianntblboeotdwoefenpaGtiDenSt6s pwaittihendtisffaenrednctognratrdoelss o(FfiAguDr,et1h)e. differences being statistically significant between GDS6 patients and controls (Figure 1)

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Summary

Introduction

Alzheimer’s disease (AD) is a progressive, irreversible, neurodegenerative disorder and one of the most common causes of dementia in old age. AD currently affects about 35 million people in the world [1]. The Global Deterioration Scale (GDS) provides an indication of the seven different stages of cognitive function for AD patients. Stages 1–3 are the pre-dementia period and stages 4–7 correspond to the dementia step. At the beginning of stage 5, the individual needs assistance [2]. The neurodegeneration produced in AD might originate from the accumulation of amyloid β-peptide (Aβ) in the brain, and it is the primary influence driving AD pathogenesis. The rest of the disease process, including formation of neurofibrillary tangles containing tau protein, has been proposed as the result from an imbalance between Aβ production and clearance [3]. In AD, the ability of synapses to transmit information is reduced, the number of synapses is decreased, and death of the neurons occurs [4]

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