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Age-related reduction in brain ACE-2 is not exacerbated by Alzheimer's disease pathology in mouse models of Alzheimer's disease.
MacLachlan, Robert; Evans, Charles E; Chai, Siew Yeen; Good, Mark A; Kehoe, Patrick Gavin; Miners, J Scott.
Afiliación
  • MacLachlan R; Dementia Research Group, Clinical Neurosciences, Bristol Medical School, University of Bristol, Learning and Research Building, Southmead Hospital, BS10 5NB, United Kingdom.
  • Evans CE; School of Psychology, Cardiff University, Cardiff CF10 3AT, United Kingdom.
  • Chai SY; Monash Biomedicine Discovery Institute, Department of Physiology, Monash University, Clayton, Victoria 3800, Australia.
  • Good MA; School of Psychology, Cardiff University, Cardiff CF10 3AT, United Kingdom.
  • Kehoe PG; Dementia Research Group, Clinical Neurosciences, Bristol Medical School, University of Bristol, Learning and Research Building, Southmead Hospital, BS10 5NB, United Kingdom.
  • Miners JS; Dementia Research Group, Clinical Neurosciences, Bristol Medical School, University of Bristol, Learning and Research Building, Southmead Hospital, BS10 5NB, United Kingdom.
Aging Brain ; 3: 100062, 2023.
Article en En | MEDLINE | ID: mdl-36911263
An imbalance in the circulatory and organ-specific renin-angiotensin system (RAS) pathways is associated with age-related dysfunction and disease including cardiovascular burden and more recently Alzheimer's disease (AD). It is currently unclear whether an age-associated imbalance in components of the RAS within the brain precedes the onset of AD or whether a RAS imbalance is associated with the onset of disease pathology and cognitive decline. Angiotensin-converting enzyme-1 (ACE-1) and -2 (ACE-2) protein (ELISA) and enzyme activity (FRET assay), markers of the classical and counter-regulatory RAS axis respectively, and Ang-II and Ang-(1-7) peptide levels (ELISA), were measured in the left cortex across four transgenic AD mouse models of amyloid pathology (5xFAD - 2, 6, and 12 months of age; Apd9 - 3-4, 12, and 18 months of age; Tg2576 - 3-4 and 24 months of age; and PDAPP - 3-4, 7, 11, 15, and 18 months of age) and littermate wild-type (WT) controls. ACE-1 level, and enzyme activity, was unaltered in relation to age in WT mice and across all four models. In contrast, ACE-2 level and enzyme activity, was reduced and Ang-II increased with ageing in both WT animals and disease models. The changes in ACE-2 and Ang-II in AD models mirrored WT mice, except for the 5xFAD model, when the reduction in ACE-2 (and elevated Ang-II) was observed at a younger age. These data indicate an age-related dysregulation of brain RAS is likely to be driven by a reduction in ACE-2. The reduction in ACE-2 occurs at a young age, coinciding with early pathological changes and the initial deposition of Aß, and preceding neuronal loss and cognitive decline, in the transgenic AD models. However, the age-related loss was mirrored in WT mice suggesting that the change was independent of pathological Aß deposition.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Aging Brain Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Aging Brain Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Países Bajos