Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer’s disease

Suzanne E. Schindler, Yan Li, Kaitlin W. Todd, Elizabeth M. Herries, Rachel L. Henson, Julia D. Gray, Guoqiao Wang, Danielle L. Graham, Leslie M. Shaw, John Q. Trojanowski, Jason J. Hassenstab, Tammie L.S. Benzinger, Carlos Cruchaga, Mathias Jucker, Johannes Levin, Jasmeer P. Chhatwal, James M. Noble, John M. Ringman, Neill R. Graff-Radford, David M. Holtzman, Jack H. Ladenson, John C. Morris, Randall J. Bateman, Chengjie Xiong, Anne M. Fagan for the Dominantly Inherited Alzheimer Network. Alzheimer’s and Dementia 2019 Read More

Abstract

Introduction: Four less well-studied but promising “emerging” cerebrospinal fluid (CSF) biomarkers are elevated in late-onset Alzheimer disease (AD): neurogranin, synaptosomal-associated protein-25 (SNAP-25), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). Methods: CSF neurogranin, SNAP-25, VILIP-1, and YKL-40 were measured in families carrying autosomal-dominant AD mutations. Results: The four emerging CSF biomarkers were significantly elevated in the mutation carriers (n = 235) versus noncarriers (n = 145). CSF SNAP-25, VILIP-1, and YKL-40 were altered very early in the AD time course, approximately 15–19 years before estimated symptom onset. All CSF biomarkers predicted important AD-related outcomes including performance on a cognitive composite, brain amyloid burden as measured by amyloid positron emission tomography, and the estimated years from symptom onset. Discussion: Early abnormalities in CSF tTau, pTau, SNAP-25, VILIP-1, and YKL-40 suggest that synaptic damage, neuronal injury, and neuroinflammation begin shortly after the commencement of brain amyloid accumulation. © 2019 the Alzheimer’s Association

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Posted on March 13, 2019
Posted in: Clocks & Sleep, HPAN, Lysosome, Neurodegeneration, Neurogenetics & Transcriptomics, Publications Authors: , , , ,