Format

Send to

Choose Destination

See 1 citation found using an alternative search:

See comment in PubMed Commons below
Nat Neurosci. 2010 Jul;13(7):812-8. doi: 10.1038/nn.2583.

Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks.

Author information

1
Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, California, USA. jpalop@gladstone.ucsf.edu

Abstract

Alzheimer's disease is the most frequent neurodegenerative disorder and the most common cause of dementia in the elderly. Diverse lines of evidence suggest that amyloid-beta (Abeta) peptides have a causal role in its pathogenesis, but the underlying mechanisms remain uncertain. Here we discuss recent evidence that Abeta may be part of a mechanism controlling synaptic activity, acting as a positive regulator presynaptically and a negative regulator postsynaptically. The pathological accumulation of oligomeric Abeta assemblies depresses excitatory transmission at the synaptic level, but also triggers aberrant patterns of neuronal circuit activity and epileptiform discharges at the network level. Abeta-induced dysfunction of inhibitory interneurons likely increases synchrony among excitatory principal cells and contributes to the destabilization of neuronal networks. Strategies that block these Abeta effects may prevent cognitive decline in Alzheimer's disease. Potential obstacles and next steps toward this goal are discussed.

PMID:
20581818
PMCID:
PMC3072750
DOI:
10.1038/nn.2583
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center