Non-beta-amyloid/tau cerebrospinal fluid markers inform staging and progression in Alzheimer’s disease

Autor: Umesh Gangishetti, J. Christina Howell, Richard J. Perrin, Natalia Louneva, Kelly D. Watts, Alexander Kollhoff, Murray Grossman, David A. Wolk, Leslie M. Shaw, John C. Morris, John Q. Trojanowski, Anne M. Fagan, Steven E. Arnold, William T. Hu
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Alzheimer’s Research & Therapy, Vol 10, Iss 1, Pp 1-10 (2018)
Druh dokumentu: article
ISSN: 1758-9193
DOI: 10.1186/s13195-018-0426-3
Popis: Abstract Background Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by neuropathologic changes involving beta-amyloid (Aβ), tau, neuronal loss, and other associated biological events. While levels of cerebrospinal fluid (CSF) Aβ and tau peptides have enhanced the antemortem detection of AD-specific changes, these two markers poorly reflect the severity of cognitive and functional deficits in people with altered Aβ and tau levels. While multiple previous studies identified non-Aβ, non-tau proteins as candidate neurodegenerative markers to inform the A/T/N biomarker scheme of AD, few have advanced beyond association with clinical AD diagnosis. Here we analyzed nine promising neurodegenerative markers in a three-centered cohort using independent assays to identify candidates most likely to complement Aβ and tau in the A/T/N framework. Methods CSF samples from 125 subjects recruited at the three centers were exchanged such that each of the nine previously identified biomarkers can be measured at one of the three centers. Subjects were classified according to cognitive status and CSF AD biomarker profiles as having normal cognition and normal CSF (n = 31), normal cognition and CSF consistent with AD (n = 13), mild cognitive impairment and normal CSF (n = 13), mild cognitive impairment with CSF consistent with AD (n = 23), AD dementia (n = 32; CSF consistent with AD), and other non-AD dementia (n = 13; CSF not consistent with AD). Results Three biomarkers were identified to differ among the AD stages, including neurofilament light chain (NfL; p
Databáze: Directory of Open Access Journals
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