Dietary factors and Alzheimer's disease.
ABSTRACT Alzheimer's disease (AD) is increasing in prevalence, and environmental risk factors have not been identified with certainty. There is evidence that oxidative stress, homocysteine-related vitamins, fats, and alcohol have a role in the pathogenesis of AD. Few large epidemiological studies have explored the associations between nutrients and AD, and there has been only one trial of vitamin E in the prevention of AD. Some studies suggest that high intake of vitamins C, E, B6, and B12, and folate, unsaturated fatty acids, and fish are related to a low risk of AD, but reports are inconsistent. Modest to moderate alcohol intake, particularly wine, may be related to a low risk of AD. Available data do not permit definitive conclusions regarding diet and AD or specific recommendations on diet modification for the prevention of AD.
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ABSTRACT: Reduced phospholipase A2 (PLA2) activity has been reported in blood cells and in postmortem brains of patients with Alzheimer disease (AD), and there is evidence that conjugated linoleic acid (CLA) modulates the activity of PLA2 groups in non-brain tissues. As CLA isomers were shown to be actively incorporated and metabolized in the brains of rats, we hypothesized that feeding a diet naturally enriched in CLA would affect the activity and expression of Pla 2 -encoding genes in rat brain tissue, with possible implications for memory. To test this hypothesis, Wistar rats were trained for the inhibitory avoidance task and fed a commercial diet (control) or experimental diets containing either low CLA- or CLA-enriched butter for 4 weeks. After this period, the rats were tested for memory retrieval and killed for tissue collection. Hippocampal expression of 19 Pla 2 genes was evaluated by qPCR, and activities of PLA2 groups (cPLA2, iPLA2, and sPLA2) were determined by radioenzymatic assay. Rats fed the high CLA diet had increased hippocampal mRNA levels for specific PLA2 isoforms (iPla 2 g6γ; cPla 2 g4a, sPla 2 g3, sPla 2 g1b, and sPla 2 g12a) and higher enzymatic activity of all PLA2 groups as compared to those fed the control and the low CLA diet. The increment in PLA2 activities correlated significantly with memory enhancement, as assessed by increased latency in the step-down inhibitory avoidance task after 4 weeks of treatment (r s = 0.69 for iPLA2, P < 0.001; r s = 0.81 for cPLA2, P < 0.001; and r s = 0.69 for sPLA2, P < 0.001). In face of the previous reports showing reduced PLA2 activity in AD brains, the present findings suggest that dairy products enriched in cis-9, trans-11 CLA may be useful in the treatment of this disease.Journal of Neural Transmission 04/2015; DOI:10.1007/s00702-015-1401-9 · 2.87 Impact Factor
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ABSTRACT: Alzheimer's Disease (AD) is the most common age-related neurodegenerative disease, affecting an estimated 5.3 million people in the United States. While many factors likely contribute to AD progression, it is widely accepted that AD is driven by the accumulation of β-amyloid (Aβ), a small, fibrillogenic peptide generated by the sequential proteolysis of the amyloid precursor protein by the β- and γ-secretases. Though the underlying causes of Aβ accumulation in sporadic AD are myriad, it is clear that lifestyle and overall health play a significant role. The adipocyte-derived hormone leptin has varied systemic affects, including neuropeptide release and neuroprotection. A recent study by Lieb et al (2009) showed that individuals with low plasma leptin levels are at greater risk of developing AD, through unknown mechanisms. In this report, we show that plasma leptin is a strong negative predictor of Aβ levels in the mouse brain, supporting a protective role for the hormone in AD onset. We also show that the inhibition of Aβ accumulation is due to the downregulation of transcription of the γ-secretase components. On the other hand, β-secretase expression is either unchanged (BACE1) or increased (BACE2). Finally, we show that only presenilin 1 (PS1) is negatively correlated with plasma leptin at the protein level (p<0.0001). These data are intriguing and may highlight a role for leptin in regulating the onset of amyloid pathology and AD.Biochimica et Biophysica Acta 12/2012; 1832(3). DOI:10.1016/j.bbadis.2012.12.009 · 4.66 Impact Factor
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ABSTRACT: Neurosteroids and micronutrient are known to possess neuromodulator and neuroprotective activity. The present study was design to investigate the effect of 4´-chlorodiazepam (4CD) or ascorbic acid (Vit C) on Phosphamidon (PM) induced modulation of cognitive function and oxidative stress in male Wistar rats. Cognitive function was measured by using step-down latency (SDL) on a continuous avoidance apparatus and transfer latency (TL) on elevated plus maze. Oxidative stress was estimated by measuring brain malondialdehyde (MDA) level, protein carbonyl (PC) and reduced glutathione (GSH) activity. A significant reduction in both acquisition and retention in SDL was found for the PM treated group at weeks 6 and 8 as compared to control (P<0.001). PM caused a significant prolongation in both acquisition and retention in TL at 6 and 8week as compared to control (P<0.001). Two-week treatment by 4CD or Vit C antagonized the effect of PM on SDL and TL at 8th week. PM produced a statistically significant increase in the brain MDA and PC level (P<0.001) and a significant decrease in the brain GSH activity (P<0.001). Treatment with 4CD or Vit C attenuated the effect of PM on MDA, PC and GSH activity. Results of this study suggest that Vit C and 4CD have potential in reversing cognitive dysfunction and oxidative stress induced by toxicants like PM in the brain.Pharmacology Biochemistry and Behavior 11/2012; 103(3). DOI:10.1016/j.pbb.2012.10.015 · 2.82 Impact Factor