Utilidad de la cuantificación plasmática de neurosina en el diagnóstico diferencial de las demencias

Abstract

During recent years the number of studies thast describe the potential value of several proteins to diagnose or predict outcome of different types of dementias have increased exponentially. One of such markers sis neurosin (Kallikrein 6). Neurosin is a trypsin like serine-protease expressed mainly in the brain. Previous studies suggested that neurosin is a potential biomarker for Alzheimer,s disease (AD) since its levels in brain tissue, CSF, and blood appear to be altered in AD. However, the sensitiuty and specificity of plasmatic neurosin in AD and other dementias remain to be determined. To address this gap in knowledge and test the value of measuring the levels of neurosin as a diagnosis tool for MCI, AD and other dementias, we investigated the correlation between plasmatic levels of neurosin and the final diagnosis of patients with cognitive symptoms. Thus we measured plasmatic levels of neurosin in healthy individuals and patients with cognitive symptoms independently of waht the final diagnosis was. We ollected plasma samples from 228 controls and 447 patients diagnosedwith either AD, Mild Cognitive Impairment MCI),Dementia with Lewy Bodies or Parkinson-Dementia, Frontotemporal Dementia, Huntington,s disease, Primary Progressive Aphasia, Corticobasal degeneration, Creutzfeld-Jakob,s disease and Pseudodementia. Forty six MCI patients were observed for 18 months and then plasmatic neurosin wqs measured again. Plasmatic levels of neurosin increase with age in healthy individuals and decrease in patients with AD. Plasmatic levels of neurosin differ significatly between AD and Dementia with Vascular Component, Pseudodementia and the control group. Analyses comparing any other form of neurodegenerative dementia to the AD group did not show significant differences. The mean value of plamatic neurosin concentration differs significantly between MCI patients who converted to Dementia with Vascular Component, those who converted to AD, and those who remained at MCI stage. The relative risk of developing Dementia with Vascular Component when neurosin levels are higher than 5.25 ng/ml is up to 13 while the relative risk of developing mild AD when neurosin levels are lower than 5.25 ng/ml is 2. Increases in the levels of neurosin suggest progression to Dementia with Vascular Component. In conclusion, the measurement of plasmatic levels of neurosin is a useful diagnostic tool to assist in distinguishing AD patients from subjects without neurodegenerative dementia (either Pseudodementia, Vascular Dementia or controls) althoughit is not useful to distinguih different types of neurodegenerative dementias. The measurement of plasmatic neurosin concentration in patients diagnosed with MCI may predict conversion from MCI to Dementia with Vascular Compoent. A single measurement may be useful to estimate the risk of developing AD and Dementia with vascular compoent. Finally, repeated measurement of plamatic neurosin might be a useful test to prdict outcome in patients with MCI