P1‐322: Performance of Improved Cerebrospinal Fluid Aβ42 and Tau Assays in Differentiating Alzheimer's Disease and MCI from Control Subjects

The use of low Aβ42 and high Tau levels in cerebrospinal fluid (CSF) has emerged as a useful tool to enrich for mild cognitively impaired (MCI) patients at risk of progressing to dementia of the Alzheimer's type and for dementia patients likely to possess amyloid plaque and neurofibrillary tangle pathology. Use of these tests in the clinical trial setting has been challenging as the majority of assays were designed specifically as research use only (RUO) tools. The RUO tests were not designed to address significant matrix effects associated with CSF Aβ42 and lack of batch-batch robustness. The current study describes the clinical performance of improved CSF Aβ42 and Tau assays in differentiating Alzheimer's disease (AD) and MCI patients from normal controls (C). CSF samples were collected from 50 AD patients, 50 MCI patients and 50 controls. For the AD group, inclusion was based upon a probable diagnosis using NINCDS-ADRDA criteria with an MMSE between 14-23. For MCI, inclusion was based upon demonstration of an amnestic memory impairment using education adjusted scoring on the Wechsler memory Scale Revised. CSF was collected in polypropylene tubes and stored at -80C. Improved research use only kits from MSD were utilized for analysis of CSF Aβ42 and Tau per manufacturer's instructions. The control group was significantly younger than the MCI and AD groups with mean ages of 58, 67 and 70 respectively. Gender distribution was evenly matched across groups. CSF Tau levels were significantly elevated in MCI and AD compared to controls. CSF Aβ42 levels were low in AD and MCI compared to controls with significantly lower levels in AD compared to MCI. There were no significant differences in Tau between MCI and AD. Use of the ratio of Tau/Aβ42 showed good sensitivity and specificity in differentiating AD from controls with a sensitivity of 70% and specificity of 92%. Improved versions of the CSF Aβ42 and Tau assays showed good clinical performance in differentiating AD and MCI from controls. Current results are consistent with literature reporting low levels of CSF Aβ42 and high Tau in patients with AD.