Hyperleucinemia causes hippocampal retromer deficiency linking diabetes to Alzheimer's disease
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作者:
Morabito, Michael V.
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Coll Phys & Surg, Dept Pediat, Div Mol Genet, Naomi Berrie Diabet Ctr, New York, NY 10032 USAColl Phys & Surg, Dept Pediat, Div Mol Genet, Naomi Berrie Diabet Ctr, New York, NY 10032 USA
Morabito, Michael V.
[1
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Berman, Diego E.
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机构:
Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA
Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY USAColl Phys & Surg, Dept Pediat, Div Mol Genet, Naomi Berrie Diabet Ctr, New York, NY 10032 USA
Berman, Diego E.
[2
,3
]
Schneider, Remy T.
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Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USAColl Phys & Surg, Dept Pediat, Div Mol Genet, Naomi Berrie Diabet Ctr, New York, NY 10032 USA
Schneider, Remy T.
[2
]
Zhang, Yiying
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Coll Phys & Surg, Dept Pediat, Div Mol Genet, Naomi Berrie Diabet Ctr, New York, NY 10032 USAColl Phys & Surg, Dept Pediat, Div Mol Genet, Naomi Berrie Diabet Ctr, New York, NY 10032 USA
Zhang, Yiying
[1
]
Leibel, Rudolph L.
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Coll Phys & Surg, Dept Pediat, Div Mol Genet, Naomi Berrie Diabet Ctr, New York, NY 10032 USAColl Phys & Surg, Dept Pediat, Div Mol Genet, Naomi Berrie Diabet Ctr, New York, NY 10032 USA
Leibel, Rudolph L.
[1
]
Small, Scott A.
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机构:
Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA
Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USAColl Phys & Surg, Dept Pediat, Div Mol Genet, Naomi Berrie Diabet Ctr, New York, NY 10032 USA
Small, Scott A.
[2
,4
]
机构:
[1] Coll Phys & Surg, Dept Pediat, Div Mol Genet, Naomi Berrie Diabet Ctr, New York, NY 10032 USA
[2] Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA
[3] Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY USA
[4] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA
Type 2 diabetes (T2D) is a major risk factor for late-onset Alzheimer's disease (AD). A variety of metabolic changes related to T2D (e.g. hyperinsulinemia, hyperglycemia, and elevated branched-chain amino acids) have been proposed as mechanistic links, but the basis for this association remains unknown. Retromer-dependent trafficking is implicated in the pathogenesis of AD, and two key retromer proteins, VPS35 and VPS26, are deficient in the hippocampal formation of AD patients. We characterized VPS35 levels in five different mouse models of T2D/obesity to identify specific metabolic factors that could affect retromer levels in the brain. Mouse models in which hyperleucinemia was present displayed hippocampus-selective retromer deficiency. Wild-type lean mice fed a high leucine diet also developed hippocampal-selective retromer deficiency, and neuronal-like cells grown in high ambient leucine had reduced retromer complex proteins. Our results suggest that hyperleucinemia may account, in part, for the association of insulin resistance/T2D with AD. (C) 2014 Elsevier Inc. All rights reserved.
机构:
Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Muhammad, Alim
Flores, Ingrid
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Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Flores, Ingrid
Zhang, Hong
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Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Zhang, Hong
Yu, Rui
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Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Yu, Rui
Staniszewski, Agnieszka
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机构:
Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Staniszewski, Agnieszka
Planel, Emmanuel
论文数: 0引用数: 0
h-index: 0
机构:
Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Planel, Emmanuel
Herman, Mathieu
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机构:
Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Herman, Mathieu
Ho, Lingling
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Univ Wisconsin, Genet Lab, Madison, WI 53706 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Ho, Lingling
Kreber, Robert
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Univ Wisconsin, Genet Lab, Madison, WI 53706 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Kreber, Robert
Honig, Lawrence S.
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机构:
Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Honig, Lawrence S.
Ganetzky, Barry
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Univ Wisconsin, Genet Lab, Madison, WI 53706 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Ganetzky, Barry
Duff, Karen
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机构:
Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Duff, Karen
Arancio, Ottavio
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机构:
Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
Arancio, Ottavio
Small, Scott A.
论文数: 0引用数: 0
h-index: 0
机构:
Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USAUniv Wisconsin, Genet Lab, Madison, WI 53706 USA
机构:
Qingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R ChinaQingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R China
Zhang, Qiu-Yue
Tan, Meng-Shan
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Qingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R ChinaQingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R China
Tan, Meng-Shan
Yu, Jin-Tai
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机构:
Qingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R China
Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USAQingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R China
Yu, Jin-Tai
Tan, Lan
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机构:
Qingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R ChinaQingdao Univ, Sch Med, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R China
机构:
Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22904 USAUniv Virginia, Dept Biomed Engn, Charlottesville, VA 22904 USA
El-Ghazawi, Kareem
Eyo, Ukpong B.
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机构:
Univ Virginia, Ctr Brain Immunol, Dept Neurosci, Charlottesville, VA USA
Glia Sch Med, Charlottesville, VA USAUniv Virginia, Dept Biomed Engn, Charlottesville, VA 22904 USA
Eyo, Ukpong B.
Peirce, Shayn M.
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机构:
Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22904 USAUniv Virginia, Dept Biomed Engn, Charlottesville, VA 22904 USA