Reduced levels of amyloid-beta-binding proteins in cerebrospinal fluid from Alzheimer's disease patients.

Amyloid-beta(Abeta) aggregation is a major hallmark of Alzheimer's disease (AD). Previous studies have suggested that only unbound Abeta can take part in the aggregation process. Therefore, endogenous Abeta-binding proteins may have an important role in preventing AD. Here, we analyzed cerebrospinal fluid (CSF) samples from 35 subjects with AD, 18 subjects with frontotemporal dementia (FTD) and 29 non-demented controls to test if reduced Abeta-binding capacity in CSF is a specific feature of AD. A panel of known Abeta-binding CSF proteins, including beta-trace/prostaglandin D2 synthase (beta-trace), transthyretin (TTR), cystatin C (CysC) and alpha(1)-antitrypsin (AAT), were quantified and related to diagnosis and CSF levels of Abeta(1-38), Abeta(1-40) and Abeta(1-42). AD patients displayed a mild reduction in the CSF levels of beta-trace (p=0.020), CysC (p=0.017), AAT (p=0.019) and TTR (p=0.012) compared with controls. While the reductions in AAT and TTR were AD-specific, the levels of beta-trace and CysC were also reduced in FTD. As expected, CSF Abeta(1-42) was reduced in AD compared with controls (p=0.00005) and with FTD patients (p=0.015). Positive correlations between Abeta(1-42) and beta-trace, CysC and TTR, respectively, were seen only in the AD group, suggesting that deficient Abeta-binding capacity in CSF may contribute to the amyloidogenic process in AD.

Automated cerebrospinal fluid cell count--new reference ranges and evaluation of its clinical use in central nervous system infections.

OBJECTIVES: The purposes of this study were to establish new reference ranges for leukocytes in the CSF and to examine if the separation of mononuclear cells into lymphocytes and monocytes could be used to differentiate between various CNS infections that present with a similar picture in manual CSF cell counts. DESIGN AND METHODS: The automated cell counter Siemens ADVIA 2120 i was used. For the reference range section, we analyzed CSF from 80 neurologically healthy volunteers. For the differential diagnosis section we analyzed cell counts and hospital records from 175 patients with CSF mononuclear pleocytosis. RESULTS: Correlation was good between automated and manual leukocyte counts for samples with erythrocyte counts <250 cells/µL. For the neurologically healthy volunteers studied in the reference range section, the 95th percentile was 3.0 cells/µL for lymphocytes, 1.0 cell/µL for monocytes and 1.0 cell/µL for granulocytes. In the differential diagnosis section, comparisons were done between the groups Lyme neuroborreliosis and viral CNS infection. There were no significant differences between these two groups regarding cell counts; neither for lymphocytes, median 58 cells/µL vs. 72 cells/µL (P = n.s.); nor for monocytes, median 13 cells/µL vs. 16 cells/µL (P = n.s.); nor for granulocytes, median 1 cell/µL vs. 2 cells/µL (P = n.s.) CONCLUSIONS: We suggest new CSF cell count reference ranges of <4 cells/µL for lymphocytes, <3 cells/µL for monocytes and <3 cells/µL for granulocytes. The separation of mononuclear cells into lymphocytes and monocytes did not facilitate the discrimination between Lyme neuroborreliosis and viral CNS infection.