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. 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.
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. 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.
Authors: K Andersen; L J Launer; M E Dewey; L Letenneur; A Ott; J R Copeland; J F Dartigues; P Kragh-Sorensen; M Baldereschi; C Brayne; A Lobo; J M Martinez-Lage; T Stijnen; A Hofman Journal: Neurology Date: 1999-12-10 Impact factor: 9.910
Authors: Anne M Fagan; Denise Head; Aarti R Shah; Daniel Marcus; Mark Mintun; John C Morris; David M Holtzman Journal: Ann Neurol Date: 2009-02 Impact factor: 10.422
Authors: K Braunewell; P Riederer; C Spilker; E D Gundelfinger; B Bogerts; H G Bernstein Journal: Dement Geriatr Cogn Disord Date: 2001 Mar-Apr Impact factor: 2.959
Authors: W J Jagust; S M Landau; L M Shaw; J Q Trojanowski; R A Koeppe; E M Reiman; N L Foster; R C Petersen; M W Weiner; J C Price; C A Mathis Journal: Neurology Date: 2009-10-13 Impact factor: 9.910
Authors: Stephanie Jb Vos; Chengjie Xiong; Pieter Jelle Visser; Mateusz S Jasielec; Jason Hassenstab; Elizabeth A Grant; Nigel J Cairns; John C Morris; David M Holtzman; Anne M Fagan Journal: Lancet Neurol Date: 2013-09-04 Impact factor: 44.182
Authors: Maria K Lehtinen; Christopher S Bjornsson; Susan M Dymecki; Richard J Gilbertson; David M Holtzman; Edwin S Monuki Journal: J Neurosci Date: 2013-11-06 Impact factor: 6.167
Authors: David S Knopman; Samantha Budd Haeberlein; Maria C Carrillo; James A Hendrix; Geoff Kerchner; Richard Margolin; Paul Maruff; David S Miller; Gary Tong; Maria B Tome; Melissa E Murray; Peter T Nelson; Mary Sano; Niklas Mattsson; David L Sultzer; Thomas J Montine; Clifford R Jack; Hartmuth Kolb; Ronald C Petersen; Prashanthi Vemuri; Megan Zoschg Canniere; Julie A Schneider; Susan M Resnick; Gary Romano; Argonde Corien van Harten; David A Wolk; Lisa J Bain; Eric Siemers Journal: Alzheimers Dement Date: 2018-04 Impact factor: 21.566
Authors: Ross W Paterson; Jamie Toombs; Catherine F Slattery; Jonathan M Schott; Henrik Zetterberg Journal: Mol Diagn Ther Date: 2014-04 Impact factor: 4.074
Authors: Matthew R Brier; Jewell B Thomas; Anne M Fagan; Jason Hassenstab; David M Holtzman; Tammie L Benzinger; John C Morris; Beau M Ances Journal: Neurobiol Aging Date: 2013-10-18 Impact factor: 4.673