Vitamin D in Alzheimer's Disease: Low Levels in Cerebrospinal Fluid Despite Normal Amounts in Serum.

BACKGROUND: Vitamin D insufficiency has been suggested as a dementia risk factor. OBJECTIVE: In this cross-sectional, explorative study we investigated whether levels of vitamin D in cerebrospinal fluid (CSF) are lower in patients with positive biomarkers of Alzheimer's disease (AD) compared to cognitively healthy controls and whether polymorphisms of the vitamin D receptor (VDR) gene, FokI, BsmI, ApaI, and TaqI, are associated with levels of vitamin D in CSF and cognition. METHODS: We included 100 patients≥65 years assessed for cognitive impairment and 76 cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D) in both serum and CSF, and VDR polymorphisms were analyzed. RESULTS: The mean level of 25(OH)D in serum was 78.6 (SD 28.9) nmol/l. While serum levels of 25(OH)D were not significantly different between the groups, CSF levels of 25(OH)D were significantly lower in patients with positive AD core biomarkers (p = 0.001) compared to patients without such biomarkers. Individuals with the BsmI major homozygote genotype had significantly lower results on a 10-word delayed recall test (p = 0.044) and verbal fluency test (p = 0.013), and individuals with the TaqI major homozygote genotype had significantly lower results on a verbal fluency test (p = 0.030) compared to individuals with the corresponding minor homozygote genotype. CONCLUSION: Patients with positive AD core biomarkers have low CSF levels of 25(OH)D, despite sufficient serum levels. CSF levels of 25(OH)D do not seem to be affected by any of the four VDR gene polymorphisms. TaqI and BsmI major homozygote genotypes might be at increased risk for development of cognitive decline.

The Role of Brain Barriers in Maintaining Brain Vitamin Levels.

It is increasingly recognized that tissue-specific nutrient deficiencies can exist in the absence of whole-body deficiency and that these deficiencies may result from disease or disease-related physiological processes. Brain and central nervous system tissues require adequate nutrient levels to function. Many nutrients are concentrated in the cerebrospinal fluid relative to the serum in healthy individuals, and other nutrients resist depletion in the presence of whole-body nutrient depletion. The endothelial, epithelial, and arachnoid brain barriers work in concert to selectively transport, concentrate, and maintain levels of the specific nutrients required by the brain while also blocking the passage of blood-borne toxins and pathogens to brain and central nervous system tissues. These barriers preserve nutrient levels within the brain and actively concentrate nutrients within the cerebrospinal fluid and brain. The roles of physical and energetic barriers, including the blood-brain and blood-nerve barriers, in maintaining brain nutrient levels in health and disease are discussed.

In vivo vitamin C deficiency in guinea pigs increases ascorbate transporters in liver but not kidney and brain.

Moderate vitamin C (vitC) deficiency (plasma concentrations less than 23 µmol/L) affects as much as 10% of adults in the Western World and has been associated with an increased mortality in disease complexes such as cardiovascular disease and the metabolic syndrome. The distribution of vitC within the body is subjected to complex and nonlinear pharmacokinetics and largely depends on the sodium-dependent vitC-specific transporters, sodium-dependent vitamin C transporter 1 (SVCT1) and sodium-dependent vitamin C transporter 2 (SVCT2). Although currently not established, it is likely to expect that a state of deficiency may affect the expression of these transporters to preserve vitC concentrations in specific target tissues. We hypothesized that diet-induced states of vitC deficiency lead to alterations in the messenger RNA (mRNA) and/or protein expression of vitC transporters, thereby regulating vitC tissue distribution. Using guinea pigs as a validated model, this study investigated the effects of a diet-induced vitC deficiency (100 mg vitC/kg feed) or depletion (0 mg vitC/kg feed) on the expression of transporters SVCT1 and SVCT2 in selected tissues and the transport from plasma to cerebrospinal fluid (CSF). In deficient animals, SVCT1 was increased in the liver, whereas a decreased SVCT1 expression but increased SVCT2 mRNA in livers of depleted animals suggests a shift in transporter expression as response to the diet. In CSF, a constant plasma:CSF ratio shows unaltered vitC transport irrespective of dietary regime. The study adds novel information to the complex regulation maintaining vitC homeostasis in vivo during states of deficiency.

Reduced concentrations of several vitamins in normal weight patients with late-onset dementia of the Alzheimer type without vascular disease.

BACKGROUND: There is an uncertainty to what an extent initiation of late onset dementia of the Alzheimer type (DAT) is related to nutritional factors. OBJECTIVE: To find any differences in nutrient concentrations between women (75-85 y), well-nourished with moderate DAT, and a control group, all without vascular disease. DESIGN: A case control study assessing clinical, anthropometrical, biochemical and micronutrient characteristics of 20 DAT patients and 18 free-living healthy women. RESULTS: Significant differences (* = p < 0.05) were found for the following nutrients, given in sequence (Mean (SD)) for controls and DAT patients, respectively: Thiamine (nmol/L): 11.7 (6.9), 7.1(3.7)*; Blood thiamine diphosphate (nmol/L): 86.0 (12.5), 65.8 (27.5)*; Pyridoxal-5-phosphate 90.2 (14), 24.8 (3.3)*; Cobalamin (nmol/L) 435(263), 350 (264)*; Homocysteine (mmol/L) 14.7 (1.3), 18.5 (1.6)*; Ascorbic acid (mmol/L) 77.7 (28), 46.2 (25)*; alpha-tocopherol (mmol/L) 38.2 (9.2), 27.1 (11.5)*; Serum and blood thiamine mono-phosphate and ascorbic acid in cerebrospinal fluid were significantly different as well. Age, BMI, MMSE, MADRS, 'Vascular Score ' and a set of other biochemical parameters were similar between the groups. Using logistic regression analysis, models for predicting the presence of DAT all contained pyridoxal-5-phosphate, and CSF-protein, in combination with either one of variables, age, ascorbic acid, retinol, alpha-tocopherol, homocysteine, thiamin-diphosphate, CSF-thiamin. All the models give complete separation between DAT and controls. CONCLUSIONS: The presence of reduced concentrations of several vitamins in the DAT patients compared to the controls might indicate that these nutrients may contribute to the development of DAT.

Biochemical markers related to Alzheimer's dementia in serum and cerebrospinal fluid.

The diagnosis of Alzheimer's disease (AD) is currently based on clinical and neuropsychological examination. To date there is no blood test available that can discriminate dementia patients from healthy individuals. In the present paper, an overview of the current state of knowledge on biologic markers in serum (plasma) and CSF is presented. The combination of characteristic plaque markers tau and amyloid bèta may constitute a specific and sensitive CSF marker for AD. Glial fibrillary acidic protein and antibodies in CSF may be a marker for severe neurodegeneration. CSF concentrations of the oxidative stress markers 3-nitrotyrosine, 8-hydroxy-2'-deoxyguanosine and isoprostanes are increased in AD patients. Serum 24S-OH-cholesterol may be an early whereas glial fibrillary acidic protein autoantibody level may be a late marker for neurodegeneration. To date, serum alpha(1)-Antichymotripsin concentration is the most convincing marker for CNS inflammation. Increased serum homocysteine concentrations have also been consistently reported in AD. In summary, a large overlap in mean concentrations has been observed in studies comparing AD patients with healthy controls for single markers. These studies together support the theory of testing several serum markers in combination for the diagnosis of AD.