Rawan Tarawneh1,2,3, Gina D’Angelo1,4, Elizabeth Macy5, Chengjie Xiong1,4, Deborah Carter5, Nigel J. Cairns1,2,5,6,3, Anne M. Fagan1,2,3, Denise Head1,7,8, Mark A. Mintun1,2,8, Jack H. Ladenson5, Jin‐Moo Lee2,3, John C. Morris1,2,5, David M. Holtzman1,9,2,3
1Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO
2Department of Neurology, Washington University School of Medicine, St. Louis, MO
3Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO
4Division of Biostatistics, Washington University School of Medicine, St Louis, MO
5Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
6Division of Neuropathology, Washington University School of Medicine, St. Louis, MO
7Department of Psychology, Washington University School of Medicine, St. Louis, MO
8Department of Radiology, Washington University School of Medicine, St Louis, MO
9Department of Developmental Biology, Washington University School of Medicine, St Louis, MO
Tóm tắt
AbstractObjective:There is a growing need to identify cerebrospinal fluid (CSF) markers that can detect Alzheimer's disease (AD) pathology in cognitively normal individuals because it is in this population that disease‐modifying therapies may have the greatest chance of success. While AD pathology is estimated to begin ∼10–15 years prior to the onset of cognitive decline, substantial neuronal loss is present by the time the earliest signs of cognitive impairment appear. Visinin‐like protein‐1 (VILIP‐1) has demonstrated potential utility as a marker of neuronal injury. Here we investigate CSF VILIP‐1 and VILIP‐1/amyloid‐β42 (Aβ42) ratio as diagnostic and prognostic markers in early AD.Methods:We assessed CSF levels of VILIP‐1, tau, phosphorylated‐tau181 (p‐tau181), and Aβ42 in cognitively normal controls (CNC) (n = 211), individuals with early symptomatic AD (n = 98), and individuals with other dementias (n = 19). Structural magnetic resonance imaging (n = 192) and amyloid imaging with Pittsburgh Compound‐B (n = 156) were obtained in subsets of this cohort. Among the CNC cohort, 164 individuals had follow‐up annual cognitive assessments for 2–3 years.Results:CSF VILIP‐1 levels differentiated individuals with AD from CNC and individuals with other dementias. CSF VILIP‐1 levels correlated with CSF tau, p‐tau181, and brain volumes in AD. VILIP‐1 and VILIP‐1/Aβ42 predicted future cognitive impairment in CNC over the follow‐up period. Importantly, CSF VILIP‐1/Aβ42 predicted future cognitive impairment at least as well as tau/Aβ42 and p‐tau181/Aβ42.Interpretation:These findings suggest that CSF VILIP‐1 and VILIP‐1/Aβ42 offer diagnostic utility for early AD, and can predict future cognitive impairment in cognitively normal individuals similarly to tau and tau/Aβ42, respectively. ANN NEUROL 2011;
