Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of β-amyloid (Aβ 42). However, a high discrepancy between different centers in measured Aβ 42 levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured Aβ 42 level. Methods. Aliquots of CSF samples were either treated differently prior to Aβ 42 measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF Aβ 42 levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted.

BackgroundSurgery launches an inflammatory reaction in the body, as seen through increased peripheral levels of cytokines and cortisol. However, less is known about perioperative inflammatory changes in the central nervous system (CNS).Our aim was to compare inflammatory markers in serum and cerebrospinal fluid (CSF) before and after surgery and evaluate their association with measures of blood–brain barrier (BBB) integrity.MethodsThirty-five patients undergoing knee arthroplastic surgery with spinal anesthesia had CSF and serum samples drawn before, after and on the morning following surgery. Cytokines and albumin in serum and CSF and cortisol in CSF were assessed at all three points.ResultsCytokines and cortisol were significantly increased in serum and CSF after surgery (Ps <0.01) and CSF increases were greater than in serum. Ten individuals had an increased cytokine response and significantly higher CSF/serum albumin ratios (Ps <0.01), five of whom had albumin ratios in the pathological range (>11.8). Serum and CSF levels of cytokines were unrelated, but there were strong correlations between CSF IL-2, IL-10 and IL-13, and albumin ratios (Ps <0.05) following surgery.ConclusionCytokine increases in the CNS were substantially greater than in serum, indicating that the CNS inflammatory system is activated during peripheral surgery and may be regulated separately from that in the peripheral body. CSF cytokine increase may indicate sensitivity to trauma and is linked to BBB macromolecular permeability.

These results suggest an involvement of BACE1 in the MS disease process.