Molecular Mechanisms of Synaptic Disconnection in Alzheimer’s Disease

  • E. Masliah
  • M. Mallory
  • M. Alford
  • R. DeTeresa
  • A. Iwai
  • T. Saitoh
Conference paper
Part of the Research and Perspectives in Alzheimer’s Disease book series (ALZHEIMER)

Abstract

Synaptic loss and neurofibrillary pathology are major contributors to the cognitive deficits in Alzheimer’s disease (AD), indicating an altered connectivity of association neurocircuitries. Synaptic damage occurs early in the development of AD, suggesting that synapse pathology is a primary rather than a secondary event. The mechanisms of synaptic damage and neurodegeneration in AD are not completely understood. Recent studies have suggested that abnormal expression and/or processing of growth-associated proteins in the central nervous system might play a role in the mechanisms leading to synaptic damage and neurodegeneration in AD. Prominent among these proteins are amyloid precursor protein (APP), apolipoprotein E (apoE), and non Aβ amyloid component (NAC) precursor (NACP). All of these molecules have several common features: 1) modulation of synaptic function, 2) involvement in amyloidogenesis, and 3) mutations (APP) and polymorphisms (APOE, NACP) that are associated with a higher risk for AD. Abnormal functioning of synaptic-related proteins with amyloidogenic potential might play a central role in the pathogenesis of AD. In this context, the main objectives of this manuscript are to review the contribution of synaptic alterations to the mechanisms of dementia in AD and to discuss some of the possible mechanisms through which malfunctioning of APP, apoE and NACP might lead to synaptic damage and plaque formation in AD.

Keywords

Cholesterol Boron Dementia Heparin Serotonin 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • E. Masliah
    • 1
  • M. Mallory
  • M. Alford
  • R. DeTeresa
  • A. Iwai
  • T. Saitoh
  1. 1.Departments of Neurosciences and PathologyUniversity of California, San Diego, School of MedicineLa JollaUSA

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