This manuscript compares 5 commonly used CSF biomarkers in the prediction of transition between MCI and AD.  The biomarkers studied total tau, pTau231, Ab42/Ab40 ratio, and isoprostanes.  pTau231 and total tau showed comparable accuracy in predicting MCI to AD progression (83%) followed by isoprostanes (74%) and Ab42/Ab40 ratios (69%).  However, if sensitivity was held at 82%, pTau 231 had the best specificity and accuracy (80% and 80%) while the specificity and accuracy of T-tau was 70% and 74%, isoprostane was 61% and 68% and Ab42/Ab40 was 63% and 69% respectively.  Under these requirements only pTau231 exceeds the 80% threshold of sensitivity and specificity as recommended by the consensus report of the NIA Working Group on Biological Measures.

A one year longitudinal study of 8 MCI patients and 10 controls demonstrates that the ptau-231 levels increase in MCI with time after correcting for change in brain ventricular volumes (which increase in size as the disease progresses) as measured by MRI.

The study reported here is a 2-year longitudinal study of MCI patients and normal controls examining MRI in conjunction with CSF biomarkers. The study consisted of 9 normal elderly volunteers and seven MCI patients.   Patients were given MRI scans and CSF taps for biomarkers at the beginning of the study and during follow-up. ptau-231 levels were elevated in the MCI group relative to the normal group, and it what demonstrated that there was a relationship between hippocampal volume loss and elevated CSF ptau-231 indicating that ptau-231 in the CSF is a measure of loss of neurons involved in AD.   It was also demonstrated that when using a common memory examination test called the “delayed paragraph recall task” to track memory deficit in combination with ptau-231 the overall diagnostic accuracy of using the “delayed recall” test alone (63%) was increased to 88% with the addition of ptau-231.

This is an abstract of a poster presented at the European CSF symposium in 2000 by Harald Hampel.  The small study presented compares CSF biomarkers total tau, soluble gp130, neuronal thread protein, and ptau-231 in AD patients vs. healthy controls.  Of the biomarkers reported here, ptau-231 showed the best performance (100% sensitivity, 91.7% specificity).  Furthermore, levels of ptau-231 were correlated with AD progression and MCI individuals had elevated levels of ptau-231 indicative of AD.  It was concluded that ptau-231 might serve as a biomarker in the early detection of AD and in following disease progression in subjects at risk and in AD patients.

This paper documents a small study to determine if CSF ptau-231 can be used as a marker of AD progression.  Up to 7 longitudinal spinal taps were performed on 17 patients with probable AD that were not being treated with acetylcholinesterase inhibitors.  For baseline comparisons, 12 age and gender matched healthy controls were included.  At baseline, both total tau and ptau-231 were significantly elevated in AD patients over healthy controls.  Longitudinally, ptau-231 levels decreased linearly with time in AD patients, however the level of total tau did not change.  Furthermore, the rate of change of ptau-231 was correlated with the MMSE score at baseline, with a more pronounced rate of decline with advanced cognitive impairment.  This did not occur for total tau.  Collectively, the data indicates that ptau-231 can be used to monitor AD progression.  Such a marker would be particularly useful to evaluate therapeutic interventions in disease modifying drug trials.