Synapses and Alzheimer’s Disease

  1. Thomas C. Südhof3
  1. 1Department of Neuroscience, Genentech Inc., South San Francisco, California 94080
  2. 2Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115
  3. 3Howard Hughes Medical Institute, Department of Cellular and Molecular Physiology, Stanford University School of Medicine, Stanford, California 94305
  1. Correspondence: sheng.morgan{at}gene.com

Abstract

Alzheimer’s disease (AD) is a major cause of dementia in the elderly. Pathologically, AD is characterized by the accumulation of insoluble aggregates of Aβ-peptides that are proteolytic cleavage products of the amyloid-β precursor protein (“plaques”) and by insoluble filaments composed of hyperphosphorylated tau protein (“tangles”). Familial forms of AD often display increased production of Aβ peptides and/or altered activity of presenilins, the catalytic subunits of γ-secretase that produce Aβ peptides. Although the pathogenesis of AD remains unclear, recent studies have highlighted two major themes that are likely important. First, oligomeric Aβ species have strong detrimental effects on synapse function and structure, particularly on the postsynaptic side. Second, decreased presenilin function impairs synaptic transmission and promotes neurodegeneration. The mechanisms underlying these processes are beginning to be elucidated, and, although their relevance to AD remains debated, understanding these processes will likely allow new therapeutic avenues to AD.



Also in this Collection

      | Table of Contents

      This Article

      1. Cold Spring Harb. Perspect. Biol. 4: a005777 Copyright © 2012 Cold Spring Harbor Laboratory Press; all rights reserved

      Article Category

      Updates/Comments

      1. Submit Updates/Comments
      2. No Updates/Comments published

      Subject Collections

      1. The Synapse

      Share

      In this Collection