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Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice.
Giannisis, Andreas; Patra, Kalicharan; Edlund, Anna K; Nieto, Lur Agirrezabala; Benedicto-Gras, Joan; Moussaud, Simon; de la Rosa, Andrés; Twohig, Daniel; Bengtsson, Tore; Fu, Yuan; Bu, Guojun; Bial, Greg; Foquet, Lander; Hammarstedt, Christina; Strom, Stephen; Kannisto, Kristina; Raber, Jacob; Ellis, Ewa; Nielsen, Henrietta M.
Afiliação
  • Giannisis A; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 10691, Sweden.
  • Patra K; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 10691, Sweden.
  • Edlund AK; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 10691, Sweden.
  • Nieto LA; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 10691, Sweden.
  • Benedicto-Gras J; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 10691, Sweden.
  • Moussaud S; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 10691, Sweden.
  • de la Rosa A; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 10691, Sweden.
  • Twohig D; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 10691, Sweden.
  • Bengtsson T; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm, 10691, Sweden.
  • Fu Y; Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, 32224, USA.
  • Bu G; Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, 32224, USA.
  • Bial G; Yecuris Corporation, Tualatin, OR, 97062, USA.
  • Foquet L; Yecuris Corporation, Tualatin, OR, 97062, USA.
  • Hammarstedt C; Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, 17177, Sweden.
  • Strom S; Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, 17177, Sweden.
  • Kannisto K; Department of Laboratory Medicine (LABMED), Karolinska Institutet, Stockholm, 17177, Sweden.
  • Raber J; Departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, and Division of Neuroscience, ONPPRC, Oregon Health & Science University, Portland, OR, 97239, USA.
  • Ellis E; Department of Clinical Science, Intervention and Technology, (CLINTEC), Division of Transplantation surgery, Karolinska Institutet, Huddinge, 14152, Sweden.
  • Nielsen HM; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, 10691, Sweden. henrietta.nielsen@dbb.su.se.
Mol Psychiatry ; 27(8): 3533-3543, 2022 08.
Article em En | MEDLINE | ID: mdl-35418601
Liver-generated plasma apolipoprotein E (apoE) does not enter the brain but nonetheless correlates with Alzheimer's disease (AD) risk and AD biomarker levels. Carriers of APOEε4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEε4 carriers. Whether altered plasma liver-derived apoE or specifically an APOEε4 liver phenotype promotes neurodegeneration is unknown. Here we investigated the brains of Fah-/-, Rag2-/-, Il2rg-/- mice on the Non-Obese Diabetic (NOD) background (FRGN) with humanized-livers of an AD risk-associated APOE ε4/ε4 versus an APOE ε2/ε3 genotype. Reduced endogenous mouse apoE levels in the brains of APOE ε4/ε4 liver mice were accompanied by various changes in markers of synaptic integrity, neuroinflammation and insulin signaling. Plasma apoE4 levels were associated with unfavorable changes in several of the assessed markers. These results propose a previously unexplored role of the liver in the APOEε4-associated risk of neurodegenerative disease.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Neurodegenerativas / Doença de Alzheimer Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Neurodegenerativas / Doença de Alzheimer Idioma: En Ano de publicação: 2022 Tipo de documento: Article