Evidence of a role for lactadherin in Alzheimer's disease

Jacques Boddaert, Kiyoka Kinugawa, Jean Charles Lambert, Fatiha Boukhtouche, Joffrey Zoll, Régine Merval, Olivier Blanc-Brude, David Mann, Claudine Berr, José Vilar, Béatrice Garabedian, Nathalie Journiac, Dominique Charue, Jean Sébastien Silvestre, Charles Duyckaerts, Philippe Amouyel, Jean Mariani, Alain Tedgui, Ziad Mallat

    Research output: Contribution to journalArticlepeer-review

    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 β-peptide (Aβ). 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 Aβ deposition. Using surface plasmon resonance, we observed a direct protein-protein interaction between recombinant lactadherin and Aβ 1-42 peptide in vitro. Lactadherin deficiency or its neutralization using specific antibodies significantly prevented Aβ 1-42 phagocytosis by murine and human macrophages. In conclusion, lactadherin plays an important role in the phagocytosis of Aβ 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. Copyright © American Society for Investigative Pathology.
    Original languageEnglish
    Pages (from-to)921-928
    Number of pages7
    JournalAmerican journal of pathology
    Volume170
    Issue number3
    DOIs
    Publication statusPublished - Mar 2007

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