meso-zeaxanthin and Alzheimer-Disease

Alzheimer's disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD and reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age-matched control subjects before and after carotenoid supplementation. The novel oxidised phospholipid biomarker 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) was analysed using electrospray ionisation tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8-isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay. AD patients (n=21) and healthy age-matched control subjects (n=16) were supplemented with either Macushield™ (10mg meso-zeaxanthin, 10mg lutein, 2mg zeaxanthin) or placebo (sunflower oil) for six months. The MRM-MS method determined serum POVPC sensitively (from 10µl serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age-matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=-0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003). In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antioxidants; Biomarkers; Carotenoids; Cognition Disorders; Combined Modality Therapy; Dietary Supplements; Female; Humans; Lipid Peroxidation; Lutein; Male; Oxidation-Reduction; Phospholipid Ethers; Phospholipids; Reactive Oxygen Species; Zeaxanthins

Lutein and zeaxanthin are dietary carotenoids that preferentially accumulate in the macular region of the retina. Together with meso-zeaxanthin, a conversion product of lutein in the macula, they form the macular pigment. Lutein is also the predominant carotenoid in human brain tissue and lutein status is associated with cognitive function in adults. The study objective was to evaluate the relationship between retinal and brain lutein and zeaxanthin in humans.. Donated brain tissue (occipital cortex and hippocampus) and matched retina were obtained from the National Disease Research Interchange, a national human tissue resource center which adheres to strict consent and confidentiality procedures. Decedents were men and women aged >50 years who either had normal cognitive function or Alzheimer's disease. Tissues were analyzed using standard lipid extractions followed by analysis on reverse-phase high performance liquid chromatography (HPLC) and normal-phase HPLC (for meso-zeaxanthin).. Macular pigment carotenoids (lutein, meso-zeaxanthin, and zeaxanthin combined) in the retina were significantly related to the combined concentrations of lutein and zeaxanthin in the occipital cortex. When analyzed separately, only retinal lutein (plus meso-zeaxanthin), not zeaxanthin, was significantly related to lutein in the occipital cortex. No correlations were observed with lutein and zeaxanthin in the hippocampus.. Total macular pigment density measured via non-invasive, psychophysical techniques can be used as a biomarker to ascertain brain lutein and zeaxanthin status in clinical studies.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Cognition; Female; Hippocampus; Humans; Lutein; Male; Middle Aged; Neurons; Organ Specificity; Reproducibility of Results; Retina; Retinal Pigments; Tissue Banks; Visual Cortex; Zeaxanthins