Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease

Schindler, Suzanne E.; Li, Yan; Todd, Kaitlin W.; Herries, Elizabeth M.; Henson, Rachel L.; Gray, Julia D.; Wang, Guoqiao; Graham, Danielle L.; Shaw, Leslie M.; Trojanowski, John Q.; Hassenstab, Jason J.; Benzinger, Tammie L. S.; Cruchaga, Carlos; Jucker, Mathias; Levin, Johannes; Chhatwal, Jasmeer P.; Noble, James M.; Ringman, John M.; Graff-Radford, Neill R.; Holtzman, David M.; Ladenson, Jack H.; Morris, John C.; Bateman, Randall J.; Xiong, Chengjie and Fagan, Anne M. (2019): Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease. In: Alzheimers & Dementia, Vol. 15, No. 5: pp. 655-665

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 (n5235) versus noncarriers (n5145). 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. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1552-5260
• Language: English