Indiana Alzheimer Disease Center

$347,552P30FY2019AGNIH

Indiana University Indianapolis, Indianapolis IN

Investigators

Linked publications, trials & patents

Paper 39713873 Paper 39711228 Paper 39677670 Paper 39677464 Paper 39513963 Paper 39511852 Paper 39503754 Paper 39444005 Paper 39440837 Paper 39379761 Paper 39371140 Paper 39371125 Paper 39291752 Paper 39291737 Paper 39285750 Paper 39254167 Paper 39207439 Paper 39185206 Paper 39173101 Paper 39147931 Paper 39137265 Paper 39077916 Paper 38980643 Paper 38958543 Paper 38958117 Paper 38949538 Paper 38949537 Paper 38915636 Paper 38903124 Paper 38883718 Paper 38762101 Paper 38746388 Paper 38740308 Paper 38721926 Paper 38712163 Paper 38641585 Paper 38513771 Paper 38460116 Paper 38441951 Paper 38425303 Paper 38423160 Paper 38418871 Paper 38395541 Paper 38393900 Paper 38387456 Paper 38363009 Paper 38267189 Paper 38244935 Paper 38244198 Paper 38195609 Paper 38194584 Paper 38133820 Paper 38106123 Paper 38102714 Paper 38077068 Paper 38076938 Paper 38015980 Paper 38014121 Paper 38014005 Paper 38008852 Paper 38002954 Paper 38000783 Paper 37924476 Paper 37908186 Paper 37850549 Paper 37844142 Paper 37833302 Paper 37801072 Paper 37783553 Paper 37745545 Paper 37698858 Paper 37653686 Paper 37645867 Paper 37620502 Paper 37592813 Paper 37589315 Paper 37580727 Paper 37578203 Paper 37563770 Paper 37547016 Paper 37532939 Paper 37499587 Paper 37496307 Paper 37491668 Paper 37491248 Paper 37474615 Paper 37414536 Paper 37390354 Paper 37357276 Paper 37351604 Paper 37330290 Paper 37322115 Paper 37296840 Paper 37296082 Paper 37287470 Paper 37276135 Paper 37268243 Paper 37260021 Paper 37259669 Patent 7332643

Abstract

1. Abstract For many years, APOE has been the only major gene known to increase disease risk for Alzheimer disease (AD). However, genome wide association studies (GWAS) have identified over 25 loci as risk or protective factors for AD. Several of the genetic variations identified by GWAS, including changes in TREM2, are of major interest for the AD research community. The genetic information related to the brains harvested at Alzheimer Disease Centers (ADC) is of vital importance. It is necessary to expand our knowledge related to the genetics of these well characterized brains. The goal of the requested supplement for the IADC-NPC is analyzing genetically, by next- generation sequencing (NGS), a cohort of autopsy-confirmed AD cases that have been already neuropathologically characterized at the IADC. NGS is also known as high-throughput sequencing and includes whole exome sequencing (WES) and whole genome sequencing (WGS). Further neuropathologic examinations will also be performed to further analyze brain tissue?s inflammatory reaction, vulnerability of anatomical regions, and potential co-morbidities. This supplement application aims at the genetic characterization of brains from neuropathologically confirmed AD cases, currently available at the IADC. In addition to adding a new well-characterized cohort for genetic analyses, the results obtained from the proposed studies will allow us to utilize the available tissue (fixed and frozen) in more advanced studies, using novel technologies, such as confocal microscopy, mass spectrometry, and cryo-electron microscopy. Our main hypothesis is that the genetic analysis of well-characterized brain tissue may lead to the discovery of novel risk or protective genes (or variants) for AD. By deepening the knowledge of the biology of structural and genetic properties associated to pathologic CNS tissue, the brains we study will become an invaluable resource for the AD research community at-large. To accomplish our goals, we propose to isolate genomic DNA from over 350 cases stored at the NPC with a primary diagnosis of AD for NGS analysis, and to determine the presence of additional pathologies co-occurring with AD. Finally, we will associate genetic information with brain tissue (fixed and frozen) to be able to be distributed to researchers.

View original record on NIH RePORTER →