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The aldehyde dehydrogenase 2 rs671 variant enhances amyloid ß pathology.
Wang, Xia; Wang, Jiayu; Chen, Yashuang; Qian, Xiaojing; Luo, Shiqi; Wang, Xue; Ma, Chao; Ge, Wei.
Afiliación
  • Wang X; Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
  • Wang J; Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
  • Chen Y; Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
  • Qian X; Department of Human Anatomy, Histology and Embryology, Neuroscience Center, National Human Brain Bank for Development and Function, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
  • Luo S; Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
  • Wang X; Department of Human Anatomy, Histology and Embryology, Neuroscience Center, National Human Brain Bank for Development and Function, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
  • Ma C; Department of Human Anatomy, Histology and Embryology, Neuroscience Center, National Human Brain Bank for Development and Function, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China. machao@ibms.cams.cn.
  • Ge W; Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China. gewei@ibms.cams.cn.
Nat Commun ; 15(1): 2594, 2024 Mar 22.
Article en En | MEDLINE | ID: mdl-38519490
ABSTRACT
In the ALDH2 rs671 variant, a guanine changes to an adenine, resulting in a dramatic decrease in the catalytic activity of the enzyme. Population-based data are contradictory about whether this variant increases the risk of Alzheimer's disease. In East Asian populations, the prevalence of the ALDH2 rs671 variant is 30-50%, making the National Human Brain Bank for Development and Function (the largest brain bank in East Asia) an important resource to explore the link between the ALDH2 rs671 polymorphism and Alzheimer's disease pathology. Here, using 469 postmortem brains, we find that while the ALDH2 rs671 variant is associated with increased plaque deposits and a higher Aß40/42 ratio, it is not an independent risk factor for Alzheimer's disease. Mechanistically, we show that lower ALDH2 activity leads to 4-HNE accumulation in the brain. The (R)-4-HNE enantiomer adducts to residue Lys53 of C99, favoring Aß40 generation in the Golgi apparatus. Decreased ALDH2 activity also lowers inflammatory factor secretion, as well as amyloid ß phagocytosis and spread in brains of patients with Alzheimer's disease. We thus define the relationship between the ALDH2 rs671 polymorphism and amyloid ß pathology, and find that ALDH2 rs671 is a key regulator of Aß40 or Aß42 generation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Enfermedad de Alzheimer Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos beta-Amiloides / Enfermedad de Alzheimer Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido