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P2‐377: Subclinical epileptiform activity in Alzheimer's disease
Author(s) -
Vossel Keith A.,
Beagle Alexander,
Hegde Manu,
Mantle Mary,
Kirsch Heidi,
Garcia Paul,
Honma Susanne,
Findlay Anne,
Rabinovici Gil,
Jagust William,
Nagarajan Srikantan,
Miller Bruce,
Roberson Erik,
Mucke Lennart
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1087
Subject(s) - subclinical infection , epilepsy , medicine , cognition , disease , dementia , observational study , population , cognitive decline , neuroscience , comorbidity , psychology , psychiatry , environmental health
Background: Pro-inflammatory cytokines have been detected in brains of individuals with Alzheimer’s disease (AD) andmay play a significant role in the pathogenesis of AD. Our earlier reports investigated glial cell responses to LPS and A b, by upregulating the expression of cytokines TNFa, IL-1 b, and IL-6, as well as iNOS and COX-2. The present study was undertaken to investigate the therapeutic benefits of AICAR (a potent activator of AMP-activated protein kinase) in blocking the pro-oxidant/proinflammatory responses inmicroglia. Objectives: Ourmain objectives were a) to understand the activation aswell release of cytokines from activatedmicroglia in response to accumulated A b, and possible therapeutic benefits of AICAR. Methods: BV-2 microglia were used in these studies to understand LPS/ SMase/A b stimulated signaling mechanisms of NF k B pathway leading to the release of NO, ROS generation , release of inflammatory cytokine (TNFa, IL-1 b, IL-6) as well the scavenging macrophage like phagocytic functions of microglia.Results:AICAR inhibits LPS, and Smase activated cytokine release and NO production. AICAR also does promote A b phagocytosis. Further we observed a reduction in the stress signalingwith a significant lowering in p-ERK, p-p38, p-Akt (ser 473) as well as significant reduction of proteins such as p-NIK, p-IKK a/b and in p-p65 translocation. Conclusions: Microglia play an active role in triggering the immune cytokine responses in the neuro-inflammatory process ofAD. AICAR treatment effectively blocked cytokine release, A b phagocytosis by regulating NF k B pathways and perhaps is effective for therapeutics of AD.