The N-terminal domain of α-dystroglycan, released as a 38 kDa protein, is increased in cerebrospinal fluid in patients with Lyme neuroborreliosis.

α-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of α-dystroglycan may be proteolytically processed to generate a small 38 kDa protein (α-DG-N). The physiological significance of α-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that α-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of α-DG-N in CSF we examined the levels of α-DG-N and known neurodegenerative markers in CSF from patients diagnosed with Lyme neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB patients, 67% showed a significant increase of CSF α-DG-N compared to healthy controls. After treatment with antibiotics the CSF α-DG-N levels were normalized in the LNB patients.

Secretion of N-terminal domain of α-dystroglycan in cerebrospinal fluid.

α-Dystroglycan (α-DG) plays crucial roles in maintaining the stability of cells. We demonstrated previously that the N-terminal domain of α-DG (α-DG-N) is secreted by cultured cells into the culture medium. In the present study, to clarify its function in vivo, we generated a monoclonal antibody against α-DG-N and investigated the secretion of α-DG-N in human cerebrospinal fluid (CSF). Interestingly, we found that a considerable amount of α-DG-N was present in CSF. α-DG-N in CSF was a sialylated glycoprotein with both N- and O-linked glycan. These observations suggest that secreted α-DG-N may be transported via CSF and have yet unidentified effects on the nervous system.

Neuronal pentraxin receptor in cerebrospinal fluid as a potential biomarker for neurodegenerative diseases.

Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by progressive loss of cognitive function, dementia, and problems with movements. In order to find new protein biomarkers of high specificity from cerebrospinal fluid (CSF) of AD and PD patients, one-dimensional gel electrophoresis (1-DE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) as well as 2-DE analysis were performed. In 1-DE and LC-MS/MS 371 proteins were identified, among which levels of proteins such as isoform 1 of contactin-1, contactin-2, carnosine dipeptidase 1 (CNDP1), 120 kDa isoform precursor of neural cell adhesion molecule 1 (NCAM-120), alpha-dystroglycan, secreted protein acidic and rich in cysteine-like protein 1 precursor (SPARCL1), isoform 2 of calsyntenin 1 (CLSTN1), and neuronal pentraxin receptor (NPR) showed significant changes in AD or PD CSF compared with normal subjects. In 2-DE analysis approximately 747-915 spots were detected in CSF of AD or PD patients, from which 17-24 proteins with more than a 1.2 fold change were identified by tandem MS. Most proteins identified showed consistent changes in LC-MS/MS and 2-DE analysis. Three proteins that showed significant changes were selected for further validation by Western blot analysis. While NCAM-120 and alpha-dystroglycan exhibited higher levels in both AD and PD CSF compared with normal subjects, the level of NPR was increased only in AD CSF in Western blot analysis. The results were consistent with quantitative analysis of 2-DE spots. A higher level of NPR was also found in AD serum. This study suggests that NCAM-120, alpha-dystroglycan, and NPR are candidate biomarkers in CSF for neurodegenerative diseases, and that the changes in the CSF level of NPR may be specific for AD.