title: Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Rawan
authors.initials: R
authors.lastname: Tarawneh
authors.forename: Gina
authors.initials: G
authors.lastname: D'Angelo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macy
authors.forename: Chengjie
authors.initials: C
authors.lastname: Xiong
authors.forename: Deborah
authors.initials: D
authors.lastname: Carter
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.forename: Denise
authors.initials: D
authors.lastname: Head
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
authors.forename: Jack H
authors.initials: JH
authors.lastname: Ladenson
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D051596:Neurocalcin / Q000097:blood / Q000134:cerebrospinal fluid*; D011379:Prognosis; D012372:ROC Curve; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D051596:Neurocalcin; D016875:tau Proteins