Chapter 21 - Trophic Factors and Cell Adhesion Molecules Can Drive Dysfunctional Plasticity and Senile Plaque Formation in Alzheimer's Disease through a Breakdown in Spatial and Temporal Regulation

Abstract

This chapter discusses the role of trophic factors and cell adhesion molecules in brain plasticity and explores the hypothesis that these molecules contribute to the development of age-related pathology in Alzheimer's disease (AD). The trophic molecules play a significant role in the process of plaque formation and β-amyloid and amyloid precursor protein (APP) are involved in attracting neurites and are responsible for their toxicity. Some of these molecules include fibroblast growth factor (bFGF), heparan sulfate proteoglycans, and the cell adhesion molecule—amyloid precursor protein (APP). Common plasticity mechanisms may be activated by divergent insults, but converge into a positive feedback cascade that induces further degeneration, programmed cell death, and further inflammation. The potential therapeutic role for growth factors in modulating the progression of AD is examined. β-amyloid, which is derived from APP, appears to have the ability to serve as a pseudo cell-adhesion molecule. When β-amyloid assembles into fibrils and develops a β-sheet conformation, it induces in neuronal processes the morphological features of dystrophic neurites in and around senile plaques.