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P4‐312: Lifetime Diet And Cognitive Performance In An Older Community‐dwelling Population
Author(s) -
Hosking Diane E.,
Danthiir Vanessa,
Nettelbeck Ted,
Wilson Carlene
Publication year - 2009
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.2009.07.091
Subject(s) - cognition , mediterranean diet , cognitive decline , gerontology , effects of sleep deprivation on cognitive performance , confirmatory factor analysis , psychology , population , cognitive test , demography , perception , medicine , environmental health , structural equation modeling , disease , dementia , psychiatry , statistics , mathematics , pathology , sociology , neuroscience
specific concentration range neuroprotective effectiveness in ex vivo tissue model. Objective: To apply computational methodologies for rapid screening of potential neuroprotective therapeutic targets induced in response to IL-1a signaling. Methods: We have performed computational modeling of IL-1/NF-kB pathway by initiating functional diagram of interactions based on cumulative literature data and their subsequent transformations into modular subgroups for application using MatLab software. We have subsequently analyzed functional output diagrams showing connectivity points based on synchrony in time-course oscillations among individual network components, such as NF-kB, IKK, IkB. While IKK appears as major controller module after neuroinflammatory activation of IL-1/IL-1R/IRAK/ TRAF pathway, number of other molecular time-responses are observed. Analysis of dynamics in NF-kB oscillations and response of interlinking adaptor and effector proteins showed profound effect on TRAF and IKK complexes, and most particularly, rapid downregulating inhibitory effect on cellular expression of MyD88. Conclusion: Our data demonstrate general beneficial and limiting usefulness of computational approaches in studies of signal transduction in AD. Using IL-1 pathway, we present sequential timedependent analysis for individual components activated in response to neuroinflammatory stimulus. We identify MyD88 as novel target with therapeutic relevance. Since complete inhibition of IL-1a by immunosuppressive, antiinflammatory NSAID treatments does not appear beneficial, likely due to disruption of neuroprotective IL-1 regulating effect on microglial chemotaxis, our study implies that fine mapping of individual factors in IL-1a signaling, such as MyD88, may provide, by targeting beneficial targets in inflammatory cascades, an improvement to the existing treatments, including Ab antibody based immunization. Acknowledgment: Alzheimer’s Association (O.M.).