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

Abstract

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.

Keywords: Alzheimer's disease; Amyloid-β; Biomarkers; Cerebrospinal fluid; Mild cognitive impairment; Tau protein.

Fig. 1

Distribution of subjects according to the values of T-tau (x-axis) and Aβ_1–42/P-tau ratio (y-axis) in the whole sample (A) and in the subsample of patients with MCI (B) taking into account the longitudinal change in diagnostic status, i.e., conversion to dementia (MCI-AD) or stability of MCI diagnosis (MCI-S). Abbreviations: T-tau, total tau; Aβ_1–42, amyloid-beta peptide; P-tau, ¹⁸¹Thr-phosphorylated-tau; MCI, mild cognitive impairment; MCI-AD, MCI subjects who progressed to Alzheimer's disease.

Fig. 2

Scatter plot of the “pathologic signature 1” for the whole sample (A) and for the subsample of patients with MCI according to conversion status (B). Abbreviations: MCI, mild cognitive impairment; MCI-AD, MCI subjects who progressed to Alzheimer's disease; MCI-S, stable cases of MCI.

Fig. 3

Kaplan-Meier curve for MCI subjects according to the “pathologic signature 1” (pathologic signature 1: Aβ_1–42 <416.0 and Aβ_1–42/P-tau <9.53). Abbreviations: MCI, mild cognitive impairment; Aβ_1–42, amyloid-beta peptide; P-tau, ¹⁸¹Thr-phophorylated-tau; AD, Alzheimer's disease.