Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE) in Alzheimer's disease
Introduction
In Alzheimer's disease (AD), amyloid-beta 1–42 (Aβ42), total protein Tau (T-tau) and hyperphosphorylated Tau (P-tau) are the clinically solely applied biomarkers [1]. As the formation of neurofibrillary tangles leading to elevations of CSF-levels of T-tau and P-tau and the formation of plaques resulting in reduced CSF-levels of Aβ42 are regarded as ‘hallmarks of AD pathology’, CSF examinations are diagnostically relevant [2] in the discrimination between different types of dementia [3] and to other psychiatric diseases like major depressive disorder (MDD) [4], [5].
A protein derived from neurons and neuroendocrine cells and involved in neuronal energy metabolism, axoplasmatic transport, neuroplastic pathways and cell survival, and used as a marker for neuronal density is the cytoplasmatic γ-isoenzyme of the glycolytic enzyme neuron-specific enolase (NSE) [6], [7], [8], [9]. Physiologically not secreted into the extracellular space, increased levels in CSF are found after neuronal damage in stroke, haemorrhage and trauma, and regarded to depict leakage or metabolic upregulation that follows increased energy demand [10], [11], [12]. Reduced levels as in multiple sclerosis, on the other hand, are regarded to depict reduced neuronal metabolic activity [13].
Investigations on NSE in the CSF in AD, however, revealed inconsistent findings with elevated levels suggesting NSE as biomarker for AD [14], elevated levels in both AD and vascular dementia as non-disease-specific marker for neuronal degeneration in dementia [15], severity-dependent levels [16], but also unaffected [17], [18] or even reduced levels [19]. Therefore, in order to investigate the potential of NSE to serve as clinical marker for neuronal turnover in AD, CSF-levels of NSE were compared between patients with AD and healthy subjects (HS) together with CSF T-tau and P-tau concentrations. We hypothesized levels of CSF-NSE to be significantly higher in AD compared to HS. Further, to the authors’ knowledge for the first time, the accuracy of CSF-NSE alone and in combination with T-tau and P-tau to distinguish AD from HS was calculated exploratively.
Section snippets
Subjects
Thirty-two patients with mild to severe AD and 32 HS without any psychiatric or neurological disorder were consecutively recruited to participate in the study. All patients and HS were admitted to hospital as inpatients. Patients with AD were recruited from the Department of Psychiatry, University Hospital Leipzig, where they were admitted for diagnosis and treatment. All HS and patients or, when appointed, proxy provided formal consent to the appropriation in this clinical study. Patients or
Results
Subjects’ characteristics are depicted in Table 1.
The ANCOVA was found to be significant for diagnosis (F(1,58) = 21.61, p = 0.00002). Men and women did not significantly differ in NSE-CSF concentrations (F(1,58) = 0.22; p = 0.64). There was no significant interaction between the factors “group” and “sex” (F(1,58) = 0.63; p = 0.43). 27.1% of the total variance in CSF-NSE values were explainable by the predictor “group” while controlling for the effects of age, sex and duration of storage (partial η2 =
Discussion
In the hereby presented investigation on levels of CSF-NSE in patients with AD compared to HS, we could demonstrate NSE to be significantly elevated in AD, yielding high effect size for the group comparison. Alone and for the first time in combination with T-tau and P-tau, NSE further showed both high sensitivity and specificity to distinguish AD from HS, suggesting a clinical application of this potential biomarker. Positive correlations between NSE, T-tau and P-tau in both groups thirdly
Conclusions
Our results demonstrating an increase in CSF-NSE in AD patients compared to HS point towards NSE as a diagnostic marker in AD associated with CSF Tau protein concentration that rewards further research.
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