title: Increased plasma levels of soluble CD40, together with the decrease of TGF beta 1, as possible differential markers of Alzheimer disease.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative illness and the most frequent cause of dementia in the elderly. The identification of activated microglia within neuritic plaques, coupled with the presence of numerous inflammatory proteins, suggests that inflammation is an integral part of the pathogenetic process in AD. In the present paper we have investigated the levels of circulating inflammatory mediators as potential AD biomarkers concentrating essentially on (a) soluble CD40 (sCD40), a member of the tumor necrosis factor receptor superfamily lacking the membrane-associated endodomain by alternative splicing, and (b) transforming growth factor (TGF)-beta 1, a cytokine deeply involved in AD and playing a protective role on CNS. Decrease of TGF-beta1 in AD patients could enhance the effects of pro-inflammatory cytokines produced by activated microglia as well as the expression of factors, such as the CD40/CD40 ligand complex, by microglia and astrocytes. Total venous blood samples were obtained from 33 patients with clinical diagnosis of possible late-onset AD, 40 healthy age-matched and 11 healthy young individuals. A significant increase of sCD40 levels plasma of AD patients versus healthy controls was measured, concomitantly with a decrease in TGF-beta1 concentration. These variations, however, showed no correlation with the expression of ApoE epsilon 4 allele, which was determined in order to assess the different frequency of this risk factor between AD and control groups. Since no comparable modifications were detected in patients affected by Parkinson's disease or non-AD-based dementia, we propose that sCD40 and TGF-beta1 plasma levels might represent possible differential biomarkers of AD, and be useful pre-mortem to support the clinical diagnosis of late-onset AD.
authors.affiliation: Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mocali
authors.forename: S
authors.initials: S
authors.lastname: Cedrola
authors.forename: N
authors.initials: N
authors.lastname: Della Malva
authors.forename: M
authors.initials: M
authors.lastname: Bontempelli
authors.forename: V A M
authors.initials: VA
authors.lastname: Mitidieri
authors.forename: A
authors.initials: A
authors.lastname: Bavazzano
authors.forename: R
authors.initials: R
authors.lastname: Comolli
authors.forename: F
authors.initials: F
authors.lastname: Paoletti
authors.forename: C A M
authors.initials: CA
authors.lastname: La Porta
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D019013:CD40 Antigens / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000175:diagnosis; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053773:Transforming Growth Factor beta1
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D019013:CD40 Antigens; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1