Person:
Mably, Alexandra J

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Mably

First Name

Alexandra J

Name

Mably, Alexandra J

Filters

2013 - 20142

Settings

Author's Publications: search.filters.isAuthorOfPublication.d734dcb6-95ab-49f6-9a3c-46f89993239e

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Exosomes neutralize synaptic-plasticity-disrupting activity of Aβ assemblies in vivo
    (BioMed Central, 2013) An, Kyongman; Klyubin, Igor; Kim, Youngkyu; Jung, Jung Hoon; Mably, Alexandra J; O’Dowd, Sean T; Lynch, Timothy; Kanmert, Daniel; Lemere, Cynthia; Finan, Gina M; Park, Joon Won; Kim, Tae-Wan; Walsh, Dominic; Rowan, Michael J; Kim, Joung-Hun
    Background: Exosomes, small extracellular vesicles of endosomal origin, have been suggested to be involved in both the metabolism and aggregation of Alzheimer’s disease (AD)-associated amyloid β-protein (Aβ). Despite their ubiquitous presence and the inclusion of components which can potentially interact with Aβ, the role of exosomes in regulating synaptic dysfunction induced by Aβ has not been explored. Results: We here provide in vivo evidence that exosomes derived from N2a cells or human cerebrospinal fluid can abrogate the synaptic-plasticity-disrupting activity of both synthetic and AD brain-derived Aβ. Mechanistically, this effect involves sequestration of synaptotoxic Aβ assemblies by exosomal surface proteins such as PrPC rather than Aβ proteolysis. Conclusions: These data suggest that exosomes can counteract the inhibitory action of Aβ, which contributes to perpetual capability for synaptic plasticity.
  • Thumbnail Image
    Publication
    mGlu5 receptors and cellular prion protein mediate amyloid-β-facilitated synaptic long-term depression in vivo
    (Nature Pub. Group, 2014) Hu, Neng-Wei; Nicoll, Andrew J.; Zhang, Dainan; Mably, Alexandra J; O’Malley, Tiernan; Purro, Silvia A.; Terry, Cassandra; Collinge, John; Walsh, Dominic; Rowan, Michael J.
    NMDA-type glutamate receptors (NMDARs) are currently regarded as paramount in the potent and selective disruption of synaptic plasticity by Alzheimer’s disease amyloid β-protein (Aβ). Non-NMDAR mechanisms remain relatively unexplored. Here we describe how Aβ facilitates NMDAR-independent long-term depression of synaptic transmission in the hippocampus in vivo. Synthetic Aβ and Aβ in soluble extracts of Alzheimer’s disease brain usurp endogenous acetylcholine muscarinic receptor-dependent long-term depression, to enable long-term depression that required metabotropic glutamate-5 receptors (mGlu5Rs). We also find that mGlu5Rs are essential for Aβ-mediated inhibition of NMDAR-dependent long-term potentiation in vivo. Blocking Aβ binding to cellular prion protein with antibodies prevents the facilitation of long-term depression. Our findings uncover an overarching role for Aβ-PrPC-mGlu5R interplay in mediating both LTD facilitation and LTP inhibition, encompassing NMDAR-mediated processes that were previously considered primary.