title: Cerebrospinal Fluid Markers of Neurodegeneration and Rates of Brain Atrophy in Early Alzheimer Disease.
abstract: OBJECTIVE
  Measures of neuronal loss are likely good surrogates for clinical and radiological disease progression in Alzheimer disease (AD). Cerebrospinal fluid (CSF) markers of neuronal injury or neurodegeneration may offer usefulness in predicting disease progression and guiding outcome assessments and prognostic decisions in clinical trials of disease-modifying therapies. Visinin-like protein 1 (VILIP-1) has demonstrated potential usefulness as a marker of neuronal injury in AD.
  
  
  OBJECTIVE
  To investigate the usefulness of CSF VILIP-1, tau, p-tau181, and Aβ42 levels in predicting rates of whole-brain and regional atrophy in early AD and cognitively normal control subjects over time.
  
  
  METHODS
  Longitudinal observational study of brain atrophy in participants with early AD and cognitively normal controls. Study participants had baseline CSF biomarker measurements and longitudinal magnetic resonance imaging assessments for a mean follow-up period of 2 to 3 years. Mixed linear models assessed the ability of standardized baseline CSF biomarker measures to predict rates of whole-brain and regional atrophy over the follow-up period. The setting was The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine in St Louis. Participants (mean age, 72.6 years) were individuals with a clinical diagnosis of very mild AD (n = 23) and cognitively normal controls (n = 64) who were enrolled in longitudinal studies of healthy aging and dementia. The study dates were 2000 to 2010.
  
  
  METHODS
  Correlations between baseline CSF biomarker measures and rates of whole-brain or regional atrophy in the AD and control cohorts over the follow-up period.
  
  
  RESULTS
  Baseline CSF VILIP-1, tau, and p-tau181 levels (but not Aβ42 levels) predicted rates of whole-brain and regional atrophy in AD over the follow-up period. Baseline CSF VILIP-1 levels predicted whole-brain (P = .006), hippocampal (P = .01), and entorhinal (P = .001) atrophy rates at least as well as tau and p-tau181 in early AD. Cognitively normal controls whose CSF VILIP-1, tau, or p-tau181 levels were in the upper tercile had higher rates of whole-brain (P = .02, P = .003, and P = .02, respectively), hippocampal (P = .001, P = .01, and P = .02, respectively), and entorhinal (P = .007, P = .01, and P = .01, respectively) atrophy compared with those whose levels were in the lower 2 terciles.
  
  
  CONCLUSIONS
  Cerebrospinal fluid VILIP-1 levels predict rates of whole-brain and regional atrophy similarly to tau and p-tau181 and may provide a useful CSF biomarker surrogate for neurodegeneration in early symptomatic and preclinical AD.
authors: Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri2Hope Center for Neurological Disorders, Washington University School of Medicine in St Louis, St Louis, Missouri3The Charles F. and Joanne Knight Alzheimer's.
authors: Rawan
authors: R
authors: Tarawneh
authors: The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine in St Louis, St Louis, Missouri5Department of Radiology, Washington University School of Medicine in St Louis, St Louis, Missouri6Department of.
authors: Denise
authors: D
authors: Head
authors: Department of Psychology, Washington University School of Medicine in St Louis, St Louis, Missouri.
authors: Samantha
authors: S
authors: Allison
authors: Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri3The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine in St Louis, St Louis, Missouri.
authors: Virginia
authors: V
authors: Buckles
authors: Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri2Hope Center for Neurological Disorders, Washington University School of Medicine in St Louis, St Louis, Missouri3The Charles F. and Joanne Knight Alzheimer's.
authors: Anne M
authors: AM
authors: Fagan
authors: Department of Pathology and Immunology, Washington University School of Medicine in St Louis, St Louis, Missouri.
authors: Jack H
authors: JH
authors: Ladenson
authors: Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri3The Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine in St Louis, St Louis, Missouri7Department of.
authors: John C
authors: JC
authors: Morris
authors: Department of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri2Hope Center for Neurological Disorders, Washington University School of Medicine in St Louis, St Louis, Missouri3The Charles F. and Joanne Knight Alzheimer's.
authors: David M
authors: DM
authors: Holtzman
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001284:Atrophy / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D051596:Neurocalcin / Q000134:cerebrospinal fluid*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D051596:Neurocalcin; D010446:Peptide Fragments; C496688:VSNL1 protein, human; C075222:amyloid beta-protein (1-42); D016875:tau Proteins