Abstract
Abstract
Background
Brain aging is a major risk factor in the progression of cognitive diseases including Alzheimer’s disease (AD) and vascular dementia. We investigated a mouse model of brain aging up to 24 months old (mo).
Methods
A high field (11.7T) MRI protocol was developed to characterize specific features of brain aging including the presence of cerebral microbleeds (CMBs), morphology of grey and white matter, and tissue diffusion properties. Mice were selected from age categories of either young (3 mo), middle-aged (18 mo), or old (24 mo) and fed normal chow over the duration of the study. Mice were imaged in vivo with multimodal MRI, including conventional T2-weighted (T2W) and T2*-weighted (T2*W) imaging, followed by ex vivo diffusion-weighted imaging (DWI) and T2*W MR-microscopy to enhance the detection of microstructural features.
Results
Structural changes observed in the mouse brain with aging included reduced cortical grey matter volume and enlargement of the brain ventricles. A remarkable age-related change in the brains was the development of CMBs found starting at 18 mo and increasing in total volume at 24 mo, primarily in the thalamus. CMBs presence was confirmed with high resolution ex vivo MRI and histology. DWI detected further brain tissue changes in the aged mice including reduced fractional anisotropy, increased radial diffusion, increased mean diffusion, and changes in the white matter fibers visualized by color-coded tractography, including around a large cortical CMB.
Conclusions
The mouse is a valuable model of age-related vascular contributions to cognitive impairment and dementia (VCID). In composite, these methods and results reveal brain aging in older mice as a multifactorial process including CMBs and tissue diffusion alterations that can be well characterized by high field MRI.
Funder
National Institute on Aging
National Heart, Lung, and Blood Institute
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference74 articles.
1. Roberts AW, Ogunwole SU, Blakeslee L, Rabe MA. The population 65 years and older in the United States: 2016. New York: US Department of Commerce, Economics and Statistics Administration; 2018.
2. Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM. Monetary costs of dementia in the United States. N Engl J Med. 2013;368:1326–34.
3. Niccoli T, Partridge L. Ageing as a risk factor for disease. Curr Biol. 2012;22:R741–52.
4. Castro DM, Dillon C, Machnicki G, Allegri RF. The economic cost of Alzheimer’s disease: family or public health burden? Dement Neuropsychol. 2010;4:262–7.
5. Sweeney MD, Sagare AP, Zlokovic BV. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol. 2018;14:133–50.
Cited by
13 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献