An examination of a novel multipanel of CSF biomarkers in the Alzheimer's disease clinical and pathological continuum
Carol Van Hulle, Erin M. Jonaitis, Tobey J. Betthauser, Richard Batrla, Norbert Wild, Gwendlyn Kollmorgen, Ulf Andréasson, Ozioma C. Okonkwo, Barbara B. Bendlin, Sanjay Asthana, Cynthia M. Carlsson, Sterling C. Johnson, Henrik Zetterberg, Kaj Blennow
Abstract
Abstract Introduction This study examines the utility of a multipanel of cerebrospinal fluid (CSF) biomarkers complementing Alzheimer's disease (AD) biomarkers in a clinical research sample. We compared biomarkers across groups defined by clinical diagnosis and pTau 181 /Aβ 42 status (+/−) and explored their value in predicting cognition. Methods CSF biomarkers amyloid beta (Aβ) 42 , pTau 181 , tTau, Aβ 40 , neurogranin, neurofilament light (NfL), α‐synuclein, glial fibrillary acidic protein (GFAP), chitinase‐3‐like protein 1 (YKL‐40), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), S100 calcium binding protein B (S100B), and interleukin 6 (IL6), were measured with the NeuroToolKit (NTK) for 720 adults ages 40 to 93 years (mean age = 63.9 years, standard deviation [SD] = 9.0; 50 with dementia; 54 with mild cognitive impairment [MCI], 616 unimpaired). Results Neurodegeneration and glial activation biomarkers were elevated in pTau 181 /Aβ 42 + MCI/dementia participants relative to all pTau 181 /Aβ 42 ‐ participants. Neurodegeneration biomarkers increased with clinical severity among pTau 181 /Aβ 42 + participants and predicted worse cognitive performance. Glial activation biomarkers were unrelated to cognitive performance. Discussion The NTK contains promising markers that improve the pathophysiological characterization of AD. Neurodegeneration biomarkers beyond tTau improved statistical prediction of cognition and disease stages.