Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes

NEUROBIOLOGY OF AGING

卷:31

Article

Miklossy, Judith¹  Qing, Hong¹  Radenovic, Aleksandra²  Kis, Andras²  Vileno, Bertrand²  Laszlo, Forro²  Miller, Lisa³  Martins, Ralph N.⁴  Waeber, Gerard⁵  Mooser, Vincent⁶  Bosman, Fred⁷  Khalili, Kamel⁹  Darbinian, Nune^8,9  McGeer, Patrick L.¹ 

[1] Univ British Columbia, Kinsmen Lab Neurol Res, Vancouver, BC V6T 1Z3, Canada

[2] Swiss Fed Inst Technol, Inst Phys Complex Matter, CH-15 Lausanne, Switzerland

[3] Brookhaven Natl Lab, Natl Synchrotron Light Source, Upton, NY 11973 USA

[4] Univ Western Australia, Hollywood Private Hosp, Sch Psychiat & Clin Neurosci, Sir James McCusker Alzheimers Dis Res Unit, Perth, WA 6009, Australia

[5] CHUV Univ Hosp, Dept Internal Med, Lausanne, Switzerland

[6] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA

[7] CHU Vaudois, Univ Inst Pathol, Lausanne, Switzerland

[8] Edith Cowan Univ, Ctr Excellence Alzheimers Dis Res & Care, Churchlands, WA 6018, Australia

[9] Temple Univ, Dept Neurosci, Inst Neurovirol, Philadelphia, PA 19122 USA

关键词: Alzheimer's disease;    Amylin;    Beta amyloid;    Apolipoprotein-E;    Apolipoprotein-a;    APP;    LPS;    Type 2 diabetes;    IBI/JIP-I;    JNK-1;    Tau;    Ubiquitin;   

DOI  :  10.1016/j.neurobiolaging.2008.08.019

来源: Elsevier

【 摘 要 】

Strong epidemiologic evidence suggests an association between Alzheimer disease (AD) and type 2 diabetes To determine if amyloid beta (A beta) and hyperphosphorylated tau occurs in type 2 diabetes, pancreas tissues from 21 autopsy cases (10 type 2 diabetes and 11 controls) were analyzed APP and tau mRNAs were identified in human pancreas and in cultured insulinoma beta cells (INS-I) by RT-PCR Prominent APP and tau bands were detected by Western blotting in pancreatic extracts Aggregated A beta, hyperphosphorylated tau, ubiquitin, apolipoprotein E. apolipoprotein(a), IBI/JIP-1 and JNK1 were detected in Langerhans islets in type 2 diabetic patients A beta was co-localized with amylin in islet amyloid deposits. In situ beta sheet formation of islet amylold deposits was shown by infrared microspectroscopy (SIRMS) LPS increased APP in non-neuronal cells as well We conclude that A beta deposits and hyperphosphorylated tau are also associated with type 2 diabetes, highlighting common pathogenetic features in neurodegenerative disorders, including AD and type 2 diabetes and suggesting that A beta deposits and hyperphosphorylated tau may also occur in other organs than the brain (C) 2008 Elsevier Inc All rights reserved

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