Dataset Information

Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease.

ABSTRACT: 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-?42 (A?42) ratio as diagnostic and prognostic markers in early AD.We assessed CSF levels of VILIP-1, tau, phosphorylated-tau181 (p-tau181), and A?42 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.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/A?42 predicted future cognitive impairment in CNC over the follow-up period. Importantly, CSF VILIP-1/A?42 predicted future cognitive impairment at least as well as tau/A?42 and p-tau181/A?42.These findings suggest that CSF VILIP-1 and VILIP-1/A?42 offer diagnostic utility for early AD, and can predict future cognitive impairment in cognitively normal individuals similarly to tau and tau/A?42, respectively.

SUBMITTER: Tarawneh R

PROVIDER: S-EPMC3154071 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease.

Tarawneh Rawan R D'Angelo Gina G Macy Elizabeth E Xiong Chengjie C Carter Deborah D Cairns Nigel J NJ Fagan Anne M AM Head Denise D Mintun Mark A MA Ladenson Jack H JH Lee Jin-Moo JM Morris John C JC Holtzman David M DM

Annals of neurology 20110801 2

<h4>Objective</h4>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 (V ...[more]

PMID: 21823155

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Project description:ImportanceSynaptic loss is an early pathologic substrate of Alzheimer disease (AD). Neurogranin is a postsynaptic neuronal protein that has demonstrated utility as a cerebrospinal fluid (CSF) marker of synaptic loss in AD.ObjectiveTo investigate the diagnostic and prognostic utility of CSF neurogranin levels in a large, well-characterized cohort of individuals with symptomatic AD and cognitively normal controls.Design, setting, and participantsA cross-sectional and longitudinal observational study of cognitive decline in patients with symptomatic AD and cognitively normal controls was performed. Participants were individuals with a clinical diagnosis of early symptomatic AD and cognitively normal controls who were enrolled in longitudinal studies of aging and dementia at the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, from January 21, 2000, through March 21, 2011. Data analysis was performed from November 1, 2013, to March 31, 2015.Main outcomes and measuresCorrelations between baseline CSF biomarker levels and future cognitive decline in patients with symptomatic AD and cognitively normal controls over time.ResultsA total of 302 individuals (mean [SE] age, 73.1 [0.4] years) were included in this study (95 patients [52 women and 43 men] with AD and 207 controls [125 women and 82 men]). The CSF neurogranin levels differentiated patients with early symptomatic AD from controls with comparable diagnostic utility (mean [SE] area under the receiver operating characteristic curve, 0.71 [0.03]; 95% CI, 0.64-0.77) to the other CSF biomarkers. The CSF neurogranin levels correlated with brain atrophy (normalized whole-brain volumes: adjusted r = -0.38, P = .02; hippocampal volumes: adjusted r = -0.36, P = .03; entorhinal volumes: adjusted r = -0.46, P = .006; and parahippocampal volumes: adjusted r = -0.47, P = .005, n = 38) in AD and with amyloid load (r = 0.39, P = .02, n = 36) in preclinical AD. The CSF neurogranin levels predicted future cognitive impairment (adjusted hazard ratio, 1.89; 95% CI, 1.29-2.78; P = .001 as a continuous measure, and adjusted hazard ratio, 2.78; 95% CI, 1.13-5.99; P = .02 as a categorical measure using the 85th percentile cutoff value) in controls and rates of cognitive decline (Clinical Dementia Rating sum of boxes score: β estimate, 0.29; P = .001; global composite scores: β estimate, -0.11; P = .001; episodic memory scores: β estimate, -0.18; P < .001; and semantic memory scores: β estimate, -0.06; P = .04, n = 57) in patients with symptomatic AD over time, similarly to the CSF proteins VILIP-1, tau, and p-tau181.Conclusions and relevanceThe CSF levels of the synaptic marker neurogranin offer diagnostic and prognostic utility for early symptomatic AD that is comparable to other CSF markers of AD. Importantly, CSF neurogranin complements the collective ability of these markers to predict future cognitive decline in cognitively normal individuals and, therefore, will be a useful addition to the current panel of AD biomarkers.

Dataset Information

Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease.

Publications

Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease.

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