Synaptic function and structure in Alzheimer's disease

Peter Penzes*, Jon Eric VanLeeuwen

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Mounting evidence strongly implicates the synapse as a key site for pathogenesis in Alzheimer's disease (AD). Representing the most common cause of dementia, AD has dramatically impacted the neurological and economic health of our society. AD is a debilitating neurodegenerative disease that produces marked cognitive decline. Much data has accumulated over the past decade to suggest the amyloid ß-peptide (Aß) has a critical role in mediating AD pathology early in the disease process by perturbing synaptic efficacy. This chapter critically reviews recent research that implicates synapses as key sites of early pathogenesis in AD. Most excitatory synapses in the brain rely on dendritic spines as the sites for excitatory neurotransmission. The structure and function of dendritic spines are dynamically regulated by cellular pathways acting on the actin cytoskeleton. Numerous studies analyzing human postmortem tissue, animal models and cellular paradigms indicate that AD pathology, including recent findings of tau pathology, has a deleterious effect on the pathways governing synaptic structure and function. Based on the available evidence, the major contributing factor to AD pathology is an Aß oligomer-initiated dysregulation of synaptic plasticity, leading to dendritic spine degeneration and synaptic dysfunction. Synapse stabilizing pathways may thus represent efficacious therapeutic targets for combating AD pathology.

Original languageEnglish (US)
Title of host publicationResearch Progress in Alzheimer's Disease and Dementia (V)
PublisherNova Science Publishers, Inc.
Pages1-22
Number of pages22
ISBN (Print)9781619421929
StatePublished - Dec 1 2012

Keywords

  • Animal model
  • Circuit
  • Dendritic spine
  • Genetic
  • Glutamatergic
  • Neurodegenerative
  • Postmortem
  • Synapse

ASJC Scopus subject areas

  • Medicine(all)
  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Synaptic function and structure in Alzheimer's disease'. Together they form a unique fingerprint.

Cite this