Combined Analysis of CSF Parameters

There are many examples of CNS diseases where a combination of more than one CSF parameter significantly improves the accuracy of the diagnosis. Neuro-inflammatory diseases, like neuroborreliosis (Tumani et al., 1995) or multiple sclerosis (Reiber et al., 1998) are representative examples. Similarly, studies have been reported showing increased sensitivity and specificity of a combination of CSF parameters in early and differential diagnoses of AD. 

Correspondingly, in an international multicenter project, combined analysis of A(31-42 and tau protein showed 85% diagnostic sensitivity and 58% specificity in 

We have recently reported a decreased fraction of A 5l-42 of all A(i peptides in C S E of patients with AD. In this study, all the AD patients and none of the controls appeared below the discrimination line of 8.5%. Plotting the results of relative ratios of A(il-42 against A(il-38 showed all AD cases and none of the controls in the region with decreased A(il-42 however some AD cases had increased A 5l-38, similarly to subjects with chronic neuroinflammatoiy diseases (Wiltfang et al., 2002) (figure 14.3). This observation points to a presence of chronic (micro)-inflammatory reaction in the CNS of subjects with AD. Moreover, this report also presents evidence that severity of dementia correlates negatively with percentage but not absolute value of A(i peptides shorted at their carboxyl ends. 

In a recently published study, a combination of three CSF biomarkers, namely tau, pTaulSl and AP42, could detect incipient AD among patients fulfilling the criteria for MCI with a sensitivity of 68% (95% Cl, 45-86%) and a specificity of 97% (95% Cl, 83-100%), therefore suggesting the possibility of identifying the subgroup of patients with MCI who would eventually develop AD from those who would not, to offer early treatment for the subjects at risk (Zetterberg et al., 2003). 

Perspectives Novel Techniques to Search for AD Biomarkers -Mass Spectrometry (MS), Differential Cel Electrophoresis (DICE), and Multiplexing 

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