Cerebrospinal fluid biomarkers in Alzheimer's disease: Diagnostic accuracy and prediction of dementia

INTRODUCTION Guidelines for the use of cerebrospinal fluid (CSF) biomarkers in the diagnosis of Alzheimer's disease (AD) establish that each laboratory must use internally qualified cutoff values. We determined the concentrations of biomarkers that discriminate cases from controls and combinations that predict the progression to dementia in a Brazilian cohort. METHODS Concentrations of amyloid-beta peptide (Aβ1-42), total tau (T-tau), and (181)Thr-phosphorylated-tau (P-tau) were determined in CSF samples from 184 older adults (68 mild cognitive impairment, 41 AD, 34 non-AD cognitive impairment, and 41 controls) by the INNO-BIA AlzBio3 assay. RESULTS Cutoff values discriminating AD from controls are as follows: Aβ1-42: 416.0 pg/mL (sensitivity [SE]: 83%, specificity (SP): 70%); T-tau: 76.7 pg/mL (SE: 82%, SP: 67%); P-tau: 36.1 pg/mL (SE: 83%, SP: 49%); Aβ1-42/P-tau <9.53 (SE: 88%, SP: 78%); and Aβ1-42/T-tau <4.13 (SE: 80%; SP: 80%). Combining values Aβ1-42 <416.5 pg/mL and Aβ1-42/P-tau <9.5 best predicted the conversion in 2 years (Cox regression: hazard ratio 7.24 [2.09-25.06], P = .002, SE: 74%, Sp: 73%). DISCUSSION Our findings are in line with most of the available evidence in this field; yet, our cutoff values are different from those derived from other laboratories.