title: Elevated plasma levels of soluble CD40 in incipient Alzheimer's disease.
abstract: CD40 is a member of the tumor necrosis factor receptor super-family and has been suggested to play a role in the metabolism of beta-amyloid (Abeta) in Alzheimer's disease (AD). However, the role of CD40-signalling in incipient AD has not yet been studied. We investigated the plasma levels of soluble CD40 (sCD40) and the soluble CD40 ligand (sCD40L) at baseline in 136 subjects with mild cognitive impairment (MCI) and 30 age-matched controls. Sixty of the 136 MCI cases converted to AD (MCI-AD) during a clinical follow-up period of 4-7 years. The baseline levels of sCD40, but not sCD40L, were elevated in MCI-AD cases when compared to age-matched controls (Mann-Whitney U-test, p=0.02). However, MCI patients who were cognitively stable or developed vascular dementia during follow-up did not have significantly increased levels of sCD40 or sCD40L when compared to controls. The levels of sCD40 correlated to decreased baseline performance on mini-mental state examination (MMSE) in both controls (r(s)=-0.37, p<0.05) and MCI-AD cases (r(s)=-0.29, p<0.05). Finally, the plasma levels of sCD40 correlated with the levels of soluble amyloid precursor protein-alpha (sAPP-alpha) (r(s)=0.28, p<0.01) and sAPP-beta (r(s)=0.23, p<0.05) in cerebrospinal fluid. In conclusion, CD40-signalling might play a role in the pathogenesis of early AD.
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden.
authors.forename: Peder
authors.initials: P
authors.lastname: Buchhave
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000503:physiopathology; D019013:CD40 Antigens / Q000097:blood*; D023201:CD40 Ligand / Q000097:blood*; D003072:Cognition Disorders / Q000097:blood* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012737:Sex Factors; D012995:Solubility; D018709:Statistics, Nonparametric
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand