Format

Send to

Choose Destination
Brain Res Rev. 2011 Jun 24;67(1-2):184-92. doi: 10.1016/j.brainresrev.2011.01.003. Epub 2011 Jan 26.

Impaired regulation of synaptic actin cytoskeleton in Alzheimer's disease.

Author information

1
Department of Physiology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Ward 7-174, Chicago, IL 60611, USA. p-penzes@northwestern.edu

Abstract

Representing the most common cause of dementia, Alzheimer's disease (AD) has dramatically impacted the neurological and economic health of our society. AD is a debilitating neurodegenerative disease that produces marked cognitive decline. Much evidence has accumulated over the past decade to suggest soluble oligomers of beta-amyloid (Aβ) have a critical role in mediating AD pathology early in the disease process by perturbing synaptic efficacy. Here we critically review 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 has a deleterious effect on the pathways governing actin cytoskeleton stability. Based on the available evidence, we propose the idea that a contributing factor to synaptic pathology in early AD is an Aβ oligomer-initiated collapse of a "synaptic safety net" in spines, leading to dendritic spine degeneration and synaptic dysfunction. Spine stabilizing pathways may thus represent efficacious therapeutic targets for combating AD pathology.

PMID:
21276817
PMCID:
PMC3109125
DOI:
10.1016/j.brainresrev.2011.01.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center