title: Expression of vesicle-associated membrane-protein-associated protein B cleavage products in peripheral blood leukocytes and cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  Vesicle-associated membrane-protein-associated protein B (VAPB) is an endoplasmic reticulum (ER) resident protein participating in ER function, vesicle trafficking, calcium homeostasis and lipid transport. Its N-terminal domain, named MSP, is cleaved and secreted, serving as an extracellular ligand. VAPB mutations are linked to autosomal-dominant motor neuron diseases, including amyotrophic lateral sclerosis (ALS) type 8. An altered VAPB function is also suspected in sporadic ALS (SALS).
  
  
  METHODS
  The expression pattern of VAPB cleavage and secreted products in the peripheral blood leukocytes (PBL) and cerebrospinal fluid (CSF) of SALS patients and neurological controls was assessed. PBL from healthy controls were also analyzed. Assays were carried out through western blotting, using an anti-VAPB (N-terminal) antibody.
  
  
  RESULTS
  Two VAPB fragments containing the MSP domain (17 kDa and 14 kDa molecular sizes) were identified in PBL of SALS and controls, with no significant differences amongst groups. In CSF, only the 14 kDa VAPB MSP fragment was expressed and a corresponding VAPA fragment was not detected. The CSF VAPB fragment was absent in 58.7% of SALS patients, of whom 79.2% were bulbar onset (P = 0.001, bulbar versus spinal).
  
  
  CONCLUSIONS
  The absence of the CSF VAPB MSP fragment from most bulbar-onset SALS patients suggests a specific alteration of brain-derived VAPB cleavage and secretion in this group of patients, and hints at a role of VAPB in the pathophysiology of this motor neuron disease.
authors.affiliation: Neuroscience Unit, CNR Institute of Biomedicine and Molecular Immunology, Palermo, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Deidda
authors.forename: G
authors.initials: G
authors.lastname: Galizzi
authors.forename: R
authors.initials: R
authors.lastname: Passantino
authors.forename: C
authors.initials: C
authors.lastname: Cascio
authors.forename: D
authors.initials: D
authors.lastname: Russo
authors.forename: T
authors.initials: T
authors.lastname: Colletti
authors.forename: V
authors.initials: V
authors.lastname: La Bella
authors.forename: P
authors.initials: P
authors.lastname: Guarneri
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000473:pathology*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009154:Mutation / Q000235:genetics; D018709:Statistics, Nonparametric; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C114051:VAPA protein, human; C496748:VAPB protein, human; D033921:Vesicular Transport Proteins
keywords: amyotrophic lateral sclerosis; cerebrospinal fluid; nematode major sperm protein; peripheral blood leukocytes; proteolysis; vesicle-associated membrane-protein-associated protein A; vesicle-associated membrane-protein-associated protein B