Research Article Brain and Nerves Volume 5: 1-8 ISSN: 2515-012X Brain Nerves, 2020 doi: 10.15761/JBN.1000127 Hippocampal T2 signal loss and decreased radial arm maze performance in transgenic murine model for AD Rajan Adhikari 1,2,a , Kevin S Steed 1,3,4,a , BreAnna Hutchinson 1 *, Haonan Wang 5 , Michael Mendoza 5 , Ryan Staudte 1 , Maya Atmojo 1 , Parker Cox 1 , Ty Hancock 1 , Kyle Barkdull 1 , Matthew Harris 1 , Richard Watt 6 , Neal Bangerter 5,7 and Jonathan J Wisco 1,8,9 * 1 Department of Physiology and Developmental Biology, Neuroscience Center, Brigham Young University, Provo, UT 84602, USA 2 Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118, USA 3 California Health Sciences University College of Osteopathic Medicine, Clovis, CA 93612, USA 4 Mayo Clinic, Phoenix, AZ 85259, USA 5 Department of Electrical Engineering, Brigham Young University, Provo, UT 84602, USA 6 Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA 7 Department of Engineering, Department of Bioengineering, Imperial College, London, SW7 2AZ, UK 8 Department of Neurobiology and Anatomy, University of Utah Medical School, Salt Lake City, UT 84132, USA 9 Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA 02118, USA a Contributed equally to this project Abstract We propose that Alzheimer’s disease (AD) progression is largely caused by excess reactive oxygen species (ROS) or free radicals created by iron dysregulation. An AD brain is struggling with damage control creating harmful tau tangles and amyloid plaques to deal with the dysregulated iron. We hypothesized that transgenic APP/PS1 (Amyloid precursor protein/ Presenilin-1) and Tau mice would exhibit higher levels of deposits in the brain which can be detected through MRI as well as decreased behavioral performance in radial arm maze tasks. We bred APP/PS1 transgenic mice overexpressing chimeric mouse/human APP-695 with mutations and human PSEN1 carrying the exon-9-deleted variant (PSEN1dE9), and Tau mice overexpressing all six isoforms of hyper-phosphorylated human MAPT (Microtubule associated protein Tau), which were compared with age controlled wild type mice. Mice received a diet of either regular or methionine rich chow as an oxidative stressor. Subgroups received a rescue treatment of either zinc, metformin or clioquinol chow. MRI (Magnetic Resonance Imaging) scans were performed using a Siemens 3 Tesla scanner. Behavioral data was collected using a radial arm maze (RAM) for 2 weeks at each point. Data collection time points were: 1 (baseline), 3, 6 and 9 months. Mean T2 TSE signals from scans on these mice revealed signifcant signal loss in bilateral hippocampi when compared by age. We also found a signifcant main efect of genotype and a trend toward signifcance for genotype and treatment interaction in the mean time mice spent in the RAM. Pairwise comparison showed a signifcant diference between the time male and female mice spent in the RAM. Tere was, however, no efect of signal loss or behavior defcit when comparing rescue treatments with or without oxidative insults. Te decrease in signal and RAM performance is due to plaque increase and accompanying iron, which ofers a possibility to refne the imaging techniques in pursuit of a noninvasive diagnostic biomarker. *Correspondence to: Jonathan J Wisco, PhD, Associate Professor, Boston University School of Medicine, Department of Anatomy and Neurobiology, Laboratory for Translational Anatomy of Degenerative Diseases and Developmental Disorders (TAD4), 72 E Concord St, L-1004, Boston, MA 02118, USA, Tel: 310-746-6647/ Ofce: 617-358-2002; E-mail: jjwisco@bu.edu Key words: Alzheimer’s disease, MRI, transgenic, radial arm maze, amyloid, tau, reactive oxygen species Received: December 21, 2019; Accepted: January 03, 2020; Published: January 06, 2020 Introduction Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and progressive loss of cognitive functions that impede performance of daily activities. It is mostly seen in the elderly population and is the leading cause of dementia. Te diagnostic hallmarks of AD are the presence of amyloid beta (Aβ) plaques, neurofbrillary tangles from phosphorylated tau proteins, neurodegeneration and synapse loss [1,2] seen in post mortem brain studies. Formation of such plaques and tangles precedes, up to a decade or more, any clinical symptoms [3,4]. Tis describes the necessity of sensitive biomarkers for AD that not only help in early diagnosis but also provide information regarding responses to potential treatments that impede disease progression [5-7]. With the number of AD patients increasing steadily each year, AD is becoming a larger fnancial burden on the world’s population, as well as a psychological and emotional strain on those who live with and take care of patients struck with the disease [8]. Advances in methods for treatment and diagnosis, such as Magnetic Resonance Imaging (MRI), are extremely important for the future of patients with AD; MRI in particular, has already become a widely used tool to study AD [9,10]. Currently, however, MRI is not a perfect tool for diagnosing AD, but it does allow visualization of neuroatrophy and other artifacts not normally observable until afer autopsy [11-13]. Unfortunately, many of those artifacts are still not visible using MRI until the advanced stages