title: Evidence of a role for lactadherin in Alzheimer's disease.
abstract: Lactadherin is a secreted extracellular matrix protein expressed in phagocytes and contributes to the removal of apoptotic cells. We examined lactadherin expression in brain sections of patients with or without Alzheimer's disease and studied its role in the phagocytosis of amyloid beta-peptide (Abeta). Cells involved in Alzheimer's disease, including vascular smooth muscle cells, astrocytes, and microglia, showed a time-related increase in lactadherin production in culture. Quantitative analysis of the level of lactadherin showed a 35% reduction in lactadherin mRNA expression in the brains of patients with Alzheimer's disease (n = 52) compared with age-matched controls (n = 58; P = 0.003). Interestingly, lactadherin protein was detected in the brains of patients with Alzheimer's disease and controls, with low expression in areas rich in senile plaques and marked expression in areas without Abeta deposition. Using surface plasmon resonance, we observed a direct protein-protein interaction between recombinant lactadherin and Abeta 1-42 peptide in vitro. Lactadherin deficiency or its neutralization using specific antibodies significantly prevented Abeta 1-42 phagocytosis by murine and human macrophages. In conclusion, lactadherin plays an important role in the phagocytosis of Abeta 1-42 peptide, and its expression is reduced in Alzheimer's disease. Alterations in lactadherin production/function may contribute to the initiation and/or progression of Alzheimer's disease.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Cardiovasculaire Lariboisière, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Boddaert
authors.forename: Kiyoka
authors.initials: K
authors.lastname: Kinugawa
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.forename: Fatiha
authors.initials: F
authors.lastname: Boukhtouche
authors.forename: Joffrey
authors.initials: J
authors.lastname: Zoll
authors.forename: Régine
authors.initials: R
authors.lastname: Merval
authors.forename: Olivier
authors.initials: O
authors.lastname: Blanc-Brude
authors.forename: David
authors.initials: D
authors.lastname: Mann
authors.forename: Claudine
authors.initials: C
authors.lastname: Berr
authors.forename: José
authors.initials: J
authors.lastname: Vilar
authors.forename: Béatrice
authors.initials: B
authors.lastname: Garabedian
authors.forename: Nathalie
authors.initials: N
authors.lastname: Journiac
authors.forename: Dominique
authors.initials: D
authors.lastname: Charue
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Silvestre
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: Jean
authors.initials: J
authors.lastname: Mariani
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D017628:Microglia / Q000378:metabolism; D008894:Milk Proteins / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020349:Surface Plasmon Resonance
chemical_list: D016229:Amyloid beta-Peptides; D000954:Antigens, Surface; C098942:MFGE8 protein, human; D008894:Milk Proteins