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Cerebrospinal fluid (CSF) amyloid beta42 (Abeta42) concentrations are decreased in patients with Alzheimer disease (AD). Consequently, low Abeta42 is considered a positive biomarker for AD. Surprisingly, the mechanisms that underlie the decrease in CSF Abeta42 remain speculative. Better understanding of this biomarker is an essential step to unravel AD pathophysiology and to develop and evaluate treatment. Therefore, we systematically examined the possible reasons for the decreased CSF Abeta42 concentration in AD. Under normal conditions, Abeta42 can be degraded by proteases, taken up by microglia, or cleared from the brain interstitial fluid across the blood brain barrier. Alternatively, it can be transported to the CSF and be cleared from there. Aggregation of Abeta42 appears the most likely cause for the decreased CSF Abeta42 concentration in AD: the aggregated state inhibits Abeta42 from being transported from the ISF to the CSF. Evidence for other possibilities such as a decreased production of Abeta42, an increased proteolytic breakdown or microglial uptake of Abeta42, or an increased clearance of Abeta42 to the blood, is - at best - scarce or even absent.

Investigations on the thermophilic anaerobic treatment of high-strength wastewaters (14-65 kg COD/m(3)) are presented. Vinasse, the wastewater of alcohol distilleries, was used as an example of such wastewaters. Semicontinuously fed digestion experiments at high retention times revealed that the effluent quality of digestion at 55 degrees C is comparable with that at 30 degrees C at similar loading rates. The amount of methane formed per kilogram of vinasse drops almost linearly with increasing vinasse concentrations. This can be attributed to increasing concentrations of inhibitory compounds, resulting in increasing volatile fatty acid (VFA) concentrations in the effluent. The treatment of vinasse was also investigated using upflow anaerobic sludge blanket (UASB) reactors. Thermophilic granular sludge, cultivated on sucrose, was used as seed material. The sludge required a 4-month adaptation period, during which the size of the sludge granules decreased significantly. However, the settling characteristics remained satisfactory. After adaptation, high loading and methane generation rates could be accommodated at satisfactory treatment efficiencies, namely, 86.4 kg COD/m(3) day and 26 m(3) CH(4)(STP)/m(3) day, respectively. As in the semicontinuously fed digesters, the effluent VFA concentrations were virtually independent of the loading rates applied, indicating that the toxicity of the vinasse is more important than the loading rate in determining the efficiency of the conversion of vinasse to methane.

Differentiating dementia with Lewy bodies (DLB) from Alzheimer's Disease (AD) can be difficult because of the substantial overlap in clinical features. Since deficits in serotonergic and dopaminergic pathways seem more pronounced in DLB patients, we investigated whether cerebrospinal fluid (CSF) analysis of neurotransmitter metabolites, in addition to brain-specific proteins, may improve the differentiation between DLB and AD. We retrospectively compared CSF concentrations of the neurotransmitter metabolites homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and the brain-specific proteins total tau (t-tau), phosphorylated tau protein (p-tau), and amyloid-β42 (Aβ42) in 45 patients with AD (mean age 71.6 years; 34 (76%) men; 44 probable AD, 1 definite) and 23 patients with DLB (mean age 71.6 years; 18 (78%) men; 6 possible DLB, 16 probable, 1 definite). The concentrations of all neurotransmitter metabolites, as well as those for t-tau and p-tau protein, were significantly lower in DLB compared to AD, irrespective of the diagnostic certainty (i.e., possible or probable). The currently used combination of Aβ42, p-tau, and t-tau yielded a sensitivity of 92.9% and a specificity of 90%. The addition of MHPG resulted in an increased sensitivity of 97.6% and a specificity of 95% for the discrimination between DLB and AD. In conclusion, the combination of MHPG and the brain specific proteins t-tau, p-tau, and Aβ42 in CSF were associated with the clinical diagnosis of DLB and discriminated between AD and DLB with high diagnostic accuracy, suggesting this combination as a potential biomarker for DLB.

Amyloid-β (Aβ) is known as the most prominent core protein in Alzheimer's Disease (AD) senile plaques. Although research has focused mainly on Aβ40 and Aβ42 as potential cerebrospinal fluid (CSF) biomarkers, a range of Aβ peptides with variable lengths has been demonstrated in the brains and CSF of AD patients. Recently, it has been found that the Aβ43 peptide may be more abundant than previously assumed, could therefore play an important role in AD pathophysiology, and hence also function as putative biomarker. In this study the value of CSF Aβ43 in AD diagnosis was investigated. Aβ43 levels in CSF were highly correlated with Aβ42 levels. Furthermore, in differentiation of AD from nondemented controls and from patients with Lewy body dementia and frontotemporal dementia, Aβ43 had an equal diagnostic value as Aβ42, both as a single biomarker and in combination with total and phosphorylated tau. In conclusion, quantification of Aβ43 in CSF does not add novel diagnostic information to the differential diagnosis of AD compared to existing biomarkers.

Objective: Aim of the study was to investigate the influence of CSF Aß42, p-tau and t-tau on cognitive functioning. • Abnormal CSF biomarker concentrations may not reflect the absolute amount of neuronal damage, but merely serve as an indicator of AD pathology. Methods• Clinicians should be cautious that CSF biomarkers cannot be used in isolation to predict the severity o f cognitive impairment.

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