Agreement of cerebrospinal fluid biomarkers and amyloid-PET in a multicenter study

Abstract

Core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers have shown incomplete agreement with amyloid-positron emission tomography (PET). Our goal was to analyze the agreement between AD CSF biomarkers and amyloid-PET in a multicenter study. Retrospective multicenter study (5 centers). Participants who underwent both CSF biomarkers and amyloid-PET scan within 18 months were included. Clinical diagnoses were made according to latest diagnostic criteria by the attending clinicians. CSF Amyloid Beta1-42 (Aβ1-42, A), phosphorliated tau 181 (pTau181, T) and total tau (tTau, N) biomarkers were considered normal (-) or abnormal ( +) according to cutoffs of each center. Amyloid-PET was visually classified as positive/negative. Agreement between CSF biomarkers and amyloid-PET was analyzed by overall percent agreement (OPA). 236 participants were included (mean age 67.9 years (SD 9.1), MMSE score 24.5 (SD 4.1)). Diagnoses were mild cognitive impairment or dementia due to AD (49%), Lewy body dementia (22%), frontotemporal dementia (10%) and others (19%). Mean time between tests was 5.1 months (SD 4.1). OPA between single CSF biomarkers and amyloid-PET was 74% for Aβ1-42, 75% for pTau181, 73% for tTau. The use of biomarker ratios improved OPA: 87% for Aβ1-42/Aβ1-40 (n = 155), 88% for pTau181/Aβ1-42 (n = 94) and 82% for tTau/Aβ1-42 (n = 160). A + T + N + cases showed the highest agreement between CSF biomarkers and amyloid-PET (96%), followed by A-T-N- cases (89%). Aβ1-42/Aβ1-40 was a better marker of cerebral amyloid deposition, as identified by amyloid tracers, than Aβ1-42 alone. Combined biomarkers in CSF predicted amyloid-PET result better than single biomarkers.