Transcriptome analysis of distinct mouse strains reveals kinesin light chain-1 splicing as an amyloid-β accumulation modifier

• DOI: 10.1073/pnas.1307345111
• Publication Date: 2014-02-05T05:08:01Z
• Authors: Takashi Morihara; Noriyuki Hayashi; Mikiko Yokokoji; Hiroyasu Akatsu; Michael A. Silverman; Nobuyuki Kimura; Masahiro Sato; Yuhki Saito; Toshiharu Suzuki; Kanta Yanagida; Takashi S. Kodama; Toshihisa Tanaka; Masayasu Okochi; Shinji Tagami; Hiroaki Kazui; Takashi Kudo; Ryota Hashimoto; Naohiro Itoh; Kouhei Nishitomi; Yumi Yamaguchi-Ka...; Tatsuhiko Tsunoda; Hironori Takamura; Taiichi Katayama; Ryo Kimura; Kouzin Kamino; Yoshio Hashizume; Masatoshi Takeda
• Keywords: Amyloid (mycology)

Significance Genetic studies of common complex human diseases, including Alzheimer's disease (AD), are extremely resource-intensive and have struggled to identify genes that causal in disease. Combined with the costs inability missing heritability, particularly AD, alternate strategies warrant consideration. We devised a unique strategy combines distinct mouse strains vary naturally amyloid-β production transcriptomics kinesin light chain-1 (Klc1 ) splice variant E as modifier accumulation, causative factor AD. In AD patients, expression levels KLC1 brain were significantly higher compared unaffected individuals. The identification suggests dysfunction intracellular trafficking is