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O1‐01‐04: HAβ‐KI: A KNOCK‐IN MOUSE MODEL FOR SPORADIC ALZHEIMER'S DISEASE
Author(s) -
Baglietto-Vargas David,
Cai Lena,
Forner Stefania,
Martini Alessandra,
Trujillo-Estrada Laura,
Cunha Celia,
Mortazavi Ali,
Wood Marcelo A.,
Green Kim N.,
Macgregor Grant R.,
Tenner Andrea,
LaFerla Frank
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.2018.06.2333
Subject(s) - gene knockin , context (archaeology) , amyloid precursor protein , knockout mouse , wild type , gene , mutation , disease , biology , alzheimer's disease , medicine , genetics , pathology , mutant , paleontology
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).