title: Complement C4A and C4B Gene Copy Number Study in Alzheimer's Disease Patients.
abstract: Increasing evidence suggests the importance of neuroinflammation in the pathogenesis of Alzheimer's disease (AD), which is a complex neurodegenerative disorder. Complement activation occurs in the brain of patients with AD and seems to contribute to an important local inflammatory state. Increased expression of the fourth serum complement component 4 (C4) has been observed in AD patients in many studies. This protein has two isoforms, encoded by two genes: C4A and C4B localized to the HLA class III region. These genes exhibit copy number variations (CNVs) and this different gene copy number can influence C4 protein levels. We focalized our attention on these two genes, determining the distribution of CNVs in AD patients, compared with healthy controls, in order to analyse their possible involvement in AD pathogenesis.
  
  
  
  We investigated 191 AD patients and 300 healthy controls. The C4A and C4B copy numbers were assessed by quantitative PCR (qPCR).
  
  
  
  The results obtained showed a statistically significant increase in the number of copies for both C4A and C4B in AD patients, compared with healthy controls (p<0,001).
  
  
  
  The presence of high C4A and C4B copy numbers in AD patients could explain the increased C4 protein expression observed in AD patients, thus highlighting a possible role for C4A and C4B CNVs in the risk of developing AD.
authors.affiliation: Laboratorio di Biochimica e Genetica, S.C. Pneumologia, Fondazione IRCCS Policlinico S. Matteo di Pavia, Via Taramelli 5, 27100 Pavia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Zorzetto
authors.forename: Francesca
authors.initials: F
authors.lastname: Datturi
authors.forename: Laura
authors.initials: L
authors.lastname: Divizia
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pistono
authors.forename: Ilaria
authors.initials: I
authors.lastname: Campo
authors.forename: Annalisa
authors.initials: A
authors.lastname: De Silvestri
authors.forename: Mariaclara
authors.initials: M
authors.lastname: Cuccia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ricevuti
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D015934:Complement C4a / Q000235:genetics*; D015935:Complement C4b / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male
chemical_list: D015934:Complement C4a; D015935:Complement C4b
keywords: Alzheimer';s Disease; C4A; C4B; Complement system; inflammation.