P4‐063: NEUROVASCULAR COUPLING DEFICITS ARISE PRIOR TO COGNITIVE DYSFUNCTION IN A MOUSE MODEL OF ALZHEIMER'S DISEASE

• DOI: 10.1016/j.jalz.2018.06.2466
• Publication Date: 2018-10-22T10:09:45Z
• Authors: Candice E. Van Skike; Stacy A. Hussong; Angela B. Olson; Stephen F. Hernandez; Andy Banh; Nick DeRosa; Veronica Galvan
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Cerebrovascular dysfunction emerges prior to the onset of cognitive in Alzheimer's disease (AD)1. Specifically, patients with AD exhibit deficits neurovascular coupling (NVC, increased cerebral blood flow evoked by neuronal activation), which is recapitulated various mouse models AD. We have previously identified mammalian/mechanistic target rapamycin (mTOR) as a major driver brain vascular AD2. Therefore, aims present study were 1) establish mTOR-dependent contribution NVC mice, and 2) define mechanisms mTOR-mediated nitric oxide synthase (nNOS) insensitivity using vivo vitro techniques. Male J20 mice fed chow containing encapsulated or vehicle for either 8 months (older group only) weeks (both ages). Fear conditioning was performed at 6 12 age, followed laser Doppler flowmetery measure response whisker stimulation. In studies cultured N2A B103 neuroblastoma cell lines. old had profound impairments NVC, particularly nNOS-mediated component preserved attenuation mTOR activity treatment weeks. Further, impairments, contextual memory not significantly impaired 6MO mice. Our indicate that inhibition increases nNOS activation measured phosphorylation Ser1177. These drives loss an model, possibly inhibiting Funding: CVS: AARF-17-504221 NIA-T32AG021890. ABO: SFH: R25NS080684. VG: 1-I01-BX002211-01A2 VA Merit Award, Owens Foundation, SAMF, NIA/NIH-P30-AG013319-21 Nathan Shock Center Excellence, RL Bailey daughter LK Fund. 1. Iturria-Medina et al. Early role dysregulation on late-onset based multifactorial data-driven analysis. Nature communications. 2016. 2.Van Skike CE Galvan V. A Perfect sTORm: The Role Mammalian Target Rapamycin Dysfunction Disease. Gerontology. 2018.