Elevated cerebrospinal fluid and plasma homocysteine levels in ALS
- Authors: Agnello, L; Bazza, F; Randazzo, V; Ciaccio, M
- Publication year: 2012
- Type: Proceedings
- OA Link: http://hdl.handle.net/10447/74286
Abstract
Background: Numerous recent evidence suggests that homocysteine (HC), a putative risk factor for stroke and coronary artery disease [1,2], could play a role in the physiopathology of several neurodegenerative disorders, such as Alzheimer’s Parkinson’s diseases and amyotrophic lateral sclerosis (ALS) [3,4,5]. HC, an aminoacid involved in the methionine metabolism, acts as a neurotoxin through several mechanisms, including free radicals and cytosolic accumulation, mitochondrial dysfunctions, activation of apoptotic pathways, and excitotoxic aminoacid-mediated damage [5]. A recent report showed that plasma HC levels were significantly elevated in ALS, and in particular in those patients with a faster progression of the disease, suggesting that this endogenous molecule might represent a marker of neurodegeneration in this devastating motor neuron disorder [5]. Objectives: Aim of the study was to assay the CSF and plasma levels of HC in ALS patients and controls, and to evaluate the relationship between HC levels and clinical variables of the disease. Methods: Cerebrospinal fluid from sixty-nine (♂45, ♀24) and plasma from sixty-five ALS patients (♂42, ♀23) were taken and stored at -80° C until use. Controls (CSF = 55; plasma = 67) were patients admitted to our hospital for neurological disorders with no known relationship to HC changes. CSF and plasma from ALS patients and controls were obtained as a necessary step of the diagnostic workup. HC levels in CSF and plasma were assayed using a high performance liquid chromatograph (HPLC) and a fluorimetric detector. Results: The median level of total HC in the CSF of ALS patients was 0.46 microM, significantly higher than that of the controls (0.24 microM, +91.6%, P < 0.001). A similar trend was observed when HC was assayed in plasma (ALS, 12.4 microM vs. controls, 7.26 lM, +70.8%, P < 0.001). The CSF and plasma HC levels showed no relationship with the disease progression, age at onset, and the site of onset. Conclusions: CSF and plasma homocysteine levels were significantly increased in patients with ALS compared with controls. This enhancement seems to be independent of the vitamin levels. Our data suggest that homocysteine might represent a biochemical marker in ALS, and it might be related to the pathophysiology of the disease. References 1. Pezzini A, Del Zotto E, Padovani A. Homocysteine and cerebral ischemia: pathogenic and therapeutical implications. Curr Med Chem 2007; 14: 249–263. 2. Humphrey LL, Fu R, Rogers K, et al. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin Proc 2008; 83: 1203–1212. 3. Tchantchou F, Shea TB. Folate deprivation, the methionine cycle, and Alzheimer_s disease. Vitam Horm 2008; 79:83–97. 4. Postuma RB, Lang AE. Homocysteine and levodopa: should Parkinson disease patients receive preventative therapy? Neurology 2004; 63: 886–891. 5. Zoccolella S, Simone IL, Lamberti P, et al. Elevated plasma homocysteine levels in patients with amyotrophic lateral sclerosis. Neurology 2008; 70: 222–225.