Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE) in Alzheimer's disease

- CSF-NSE was significantly elevated in patients with AD compared to HS.
- Diagnostic sensitivity and specificity of CSF-NSE for AD vs. HS were ≥91%.
- Accuracy rates of CSF-NSE further increased in combination with T-tau and P-tau.
- High correlations between CSF-NSE and T-Tau, P-Tau in AD and HS.
- Range of biomarkers in AD may be extended with CSF-NSE.

Neuron-specific enolase (NSE) is a neuronal glycolytic enzyme of which cerebrospinal fluid (CSF) levels are found altered following acute or prolonged neuronal damage. Investigations concerning the role of NSE in Alzheimer's disease (AD) are conflicting with both elevated and reduced levels. We measured CSF-levels of NSE in 32 patients with AD and 32 healthy subjects (HS) using an electrochemiluminescence immunoassay (ECLIA). Mean levels of adjusted NSE were significantly elevated in AD (18.12 ng/mL (95% CI 15.63-20.60), HS 8.46 ng/mL (95% CI 5.98-10.94), p = 0.00002) and effect size for mean group differences high (1.84). NSE alone (cut-off score 15.80 ng/mL, 94% sensitivity, 97% specificity) and in combination with T-tau and P-Tau had high diagnostic accuracy to differentiate AD from HS. NSE correlated significantly with T-tau (r ≥ 0.87, p < 0.000001) and P-tau (r ≥ 0.88, p < 0.000001) in both AD and HS. Our results indicate elevated CSF-NSE levels to reflect altered neuronal metabolism in AD that may be used in supporting AD diagnostics.