Purpose: To formulate best estimates of sensitivity and specificity of commonly used biomarkers for identifying Alzheimer disease (AD) amongst dementia patients.
Method: Mild AD is often difficult to differentiate from mild cognitive impairment or non-AD dementias. However, making the distinction of AD is an important step to guide therapy and advise patients and caregivers. Suggested revisions to the NINDS-ADRDA criteria for diagnosing AD call for addition of one or more biomarkers. The tangles and plaques observed in AD patients are formed by excess tau filaments and amyloid protein deposits. Increased concentrations of neurofillaments and decreased concentrations of amlyoid in the cerebrospinal fluid (CSF) may be characteristic of AD. Total tau, phosphorylated tau (Ptau), and 42 amino acid form of beta-amyloid (Aβ1-42) concentration in the CSF have been studied as biomarkers for AD. A search was conducted to locate all studies of biomarkers for AD published in English from January, 1990 to March 2010. Synthesis was performed using a bivariate mixed-effects binary regression model. We calculated sensitivity (SN), specificity (SP) and the receiver operating curves (ROC), with confidence and prediction contours.
Result: Of 1840 unique studies identified, 20 presented primary data sufficient for analysis. By testing levels of tau in CSF, AD could be discriminated from non-AD dementias with a SN of 75% (95%CI 70% to 80%) and SP of 77% (95%CI 70% to 82%). The level of Ptau in CSF had a SN of 75% (95%CI 66% to 82%) and SP of 82% (95%CI 72% to 89%). The level of Aβ1-42 had a SN of 72% (95%CI 66% to 77%) and SP of 67% (95%CI 61% to 72%), while tests combining the levels of tau and Aβ1-42 resulted in SN of 80% (95%CI 72% to 85%) and SP of 76% (95%CI 57% to 88%). The area under the ROC was highest for the test of Ptau, 85% (95%CI 82% to 88%). The proportion of heterogeneity likely due to the threshold effect ranged from 17% for tau to 100% for the combined tau and Aβ1-42.
Conclusion: A combination test for Aβ1-42 and tau resulted in the highest SN, but the Ptau test had the highest SP and AUROC. Treatment profiles will determine whether more accurate SN or SP has a higher value in AD diagnosis.