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O1‐01‐05: DISTINCT NEURAL OSCILLATION ABNORMALITIES ASSOCIATED WITH AMYLOID‐BETA AND TAU IN ALZHEIMER'S DISEASE
Author(s) -
Ranasinghe Kamalini G.,
Cha Jungho,
Hinkley Leighton B.,
Beagle Alexander J.,
Mizuiri Danielle,
Honma Susanne,
Bourakova Viktoriya,
Jagust William J.,
Miller Bruce L.,
Rabinovici Gil D.,
Nagarajan Srikantan S.,
Vossel Keith A.
Publication year - 2018
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.2018.06.2334
Subject(s) - neuroscience , neurophysiology , positron emission tomography , beta (programming language) , alzheimer's disease , neuroimaging , resting state fmri , amyloid (mycology) , alpha (finance) , psychology , disease , medicine , pathology , computer science , developmental psychology , construct validity , programming language , psychometrics
significant modification of AD-relevant phenotypes compared to B6.APP/PS1 including cognitive decline, neurodegeneration, and neuroinflammation. WSB.APP/PS1 and CAST.APP/PS1 mice failed to demonstrate preference in a novel spatial recognition task, and exhibited neuronal cell loss in memory-related brain regions. Significant increases in Ab42 was accompanied by the presence of cerebral amyloid angiopathy in both CAST.APP/PS1, and more prominently, WSB.APP/PS1. Lastly, baseline myeloid cell numbers varied across the strains, and differential plaque associated response was observed in APP/PS1 mice. Conclusions:These findings challenge the currently accepted reductionist approach of examining a human mutation in a single mouse strain in order to model multifactorial diseases such as AD. These genetically diverse AD mouse models represent a unique resource to understand the biological underpinnings of AD, and lay the foundation for identifying novel therapeutic targets. igure 1. Resting-state neural synchronization patterns in patients with Alzeimer’s disease (AD) when compared to age-matchedcontrols. From top O1-01-04 HAb-KI: A KNOCK-IN MOUSE MODEL bottom each row represent the three main clinical variants of AD FOR SPORADIC ALZHEIMER’S DISEASE cluding, amnestic predominant (AD1⁄4Amn). logopenic primary progresive aphasia (AD-LPA) and posterior cortical atrophy (AD-PCA). Color aps indicate the t-values in a whole-brain voxel-wise comparison against ach AD-variant and controls, for alpha (8-12Hz) and delta-theta (2-8Hz) scillatory rhythms. Neural synchronizations within alpha band showed onsistent reductions in AD patients with unique patterns depicting phenoDavid Baglietto-Vargas, Lena Cai, Stefania Forner, Alessandra Martini, Laura Trujillo-Estrada, Celia Cunha, Ali Mortazavi, Marcelo A. Wood, Kim N. Green, Grant R.Macgregor, Andrea Tenner, Frank LaFerla, University of California Irvine, Irvine, CA, USA; University of California, Irvine, Irvine, CA, USA. Contact e-mail: d.baglietto@uci.edu pic variability of clinical variants. Neural synchronizations within deltaeta. in contrast showed increased synchrony compared to controls and ese patterns were non-specific across the clinical variants The images re thresholded with a cluster correction of 20 voxel cutoff (P<0 05) and DR10%. (n1⁄430, AD-Amn; n1⁄415, AD-LPA; n1⁄415, AD-PCA; n1⁄420, ge-matched controls).