QUANTIFICATION OF CSF Aβ1-38, TOGETHER WITH APOLIPOPROTEINS E, CAN IMPROVE THE CLINICAL DIAGNOSTIC ACCURACY FOR AD OF THE CSF TAU AND Aβ ASSAYS

Abstract

Background: Neuroinflammation contributes to several neurodegenerative diseases and might play an important role in early stages of the most common dementia, Alzheimer’s disease (AD). This study analyzed cytokine levels in cerebrospinal fluid (CSF) of patients with AD and mild cognitive impairment (MCI) and investigated their relation to established diagnostic markers of AD. Methods: CSF samples and neuropsychological data were obtained from the Clinical Neuroscience Unit. Commercial customized multiplex enzyme‘linked‘immunosorbent assays (ELISA) were used to quantify standard amyloid and tau markers and the cytokines IL‘6, IL‘18, TNF‘a, MCP‘1, MIF, MIG and IP‘10. Data was analyzed using ANOVA and linear correlation analysis adjusted for multiple testing. Results: Mild cognitive impairment (MCI) and AD patients were clearly distinguished from other neurological patients using the standard AD markers. TNF‘a was significantly elevated in the group of MCI patients. Other cytokines did not differ between patient groups, but in part correlated to age, amyloid, tau or neuropsychological markers of dementia. Conclusions: The elevation of TNF‘a in MCI indicates an involvement of this cytokine in early stages of AD. Further, several cytokines appear to correlate to disease progression and cognitive decline. It has been hypothesized that the expression of proinflammatory cytokines peaks in MCI, possibly at the point of MCI to AD turnover. Our data support this theory and indicate a need for longitudinal analysis of cytokines in CSF of individuals at risk of dementia in order to evaluate the exact time course of neuroinflammation in AD.