An examination of a novel multipanel of CSF biomarkers in the Alzheimer's disease clinical and pathological continuum

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.