Protein in Cerebrospinal Fluid May Predict Alzheimer's Progression

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Levels of VILIP-1, a brain protein, in cerebrospinal fluid may indicate progression of Alzheimer’s disease, according to a case-control trial published in JAMA Neurology.

The biomarker appeared to predict rates of whole-brain and regional atrophy, and may be a useful marker of neurodegeneration in early symptomatic and preclinical Alzheimer’s patients. The researchers also evaluated tau, p-tau181, and Aβ42.

David Holtzman, MD, of Washington University in St. Louis, and colleagues observed brain atrophy in 23 patients with early Alzheimer’s (mean age 72.6) and 64 cognitively normal adults using baseline CSF biomarker measurements and longitudinal MRI assessments for two to three years from 2000 to 2010.

Baseline levels of VILIP-1, tau, and p-tau181 predicted whole-brain and regional atrophy in Alzheimer’s but Aβ42 did not. 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 Alzheimer’s.

Among controls, those with CSF levels of VILIP-1, tau, or p-tau181 in the upper tercile had higher rates of whole-brain (P=0.02, P=0.003, and P=0.02, respectively), hippocampal (P = .001, P = .01, and P = .02, respectively), and entorhinal (P = .007, P = .01, and P = .01, respectively) atrophy than those in the lower two terciles.

The results suggest that VILIP-1 levels are predictive of whole-brain and regional atrophy similarly to tau and p-tau181 levels, and could be considered as a secondary outcome measure in clinical trials of disease-modifying drugs for mild Alzheimer’s. 

cerebrospinal fluid
Protein in Cerebrospinal Fluid May Predict Alzheimer's Progression

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.

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.

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