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Serum N -acetylaspartate Level in Amyotrophic Lateral Sclerosis

Isabella L. Simone, MD; Maddalena Ruggieri, ScB; Rosanna Tortelli, MD; Edmondo Ceci, PhD; Eustachio D’Errico, MD; Antonio Leo, MD; Stefano Zoccolella, MD; Mariangela Mastrapasqua, PhD; Rosa Capozzo, MD; Paolo Livrea, MD; Giancarlo Logroscino, MD
Arch Neurol. 2011;68(10):1308-1312. doi:10.1001/archneurol.2011.217.
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Background N -acetylaspartate (NAA) level is a biomarker of functional integrity and vitality in neurons. In vivo multisection proton (1H)–magnetic resonance spectroscopy studies indicate that NAA level decreases in specific cortical brain areas of patients with amyotrophic lateral sclerosis (ALS).

Objective To study NAA level in serum samples as a possible biomarker of ALS.

Design Serum NAA assay by liquid chromatography–mass spectrometry in a case-control series.

Setting Department of Neurological and Psychiatric Sciences, Policlinico, University of Bari, Bari, Italy.

Patients One hundred twelve consecutive patients with ALS and 51 age- and sex-matched healthy control subjects.

Main Outcome Measures General estimating equations tested associations between serum NAA level and clinical variables in patients with ALS.

Results Serum NAA level was significantly higher in ALS cases than in controls. Multivariate logistic regression analysis showed a direct association between serum NAA level and the presence of ALS. After stratifying serum NAA level based on the median value (0.171 mmol/L), the age- and sex-adjusted odds ratio for ALS was 19.97 (95% confidence interval, 7.18-55.55) (P < .001). N -acetylaspartate level did not differ across ALS clinical phenotypes. Riluzole treatment did not affect NAA level. A significant correlation was found between serum NAA level and ALS progression rate.

Conclusions High serum NAA level was found in patients with ALS, which may relate to greater excretion of NAA into the blood circulation following increased release of this metabolite from damaged neurons. The correlation between serum NAA level and disease progression rate suggests that it may be a useful biomarker of ALS.

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Figure. Serum N -acetylaspartate (NAA) levels in healthy control subjects and in patients with amyotrophic lateral sclerosis (ALS). Box represents the 25th and 75th quartiles; whiskers, range; and horizontal line in the box, the median.* P < .001.

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