Elucidating the diagnostic, therapeutic and mechanistic implications of stroke in Alzheimer’s disease
Keywords
No Thumbnail Available
Authors
Issue Date
2018-08-01
Language
en
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
By 2040, Alzheimer’s disease (AD) will affect approximately 81 million people worldwide. Studies show that hypertension, diabetes, atherosclerosis, and obesity are risk factors for both vascular disorders such as stroke and AD. Risk of both stroke and AD increases with age. Emerging evidence shows that stroke increases the risk of developing AD and in return, AD is a risk factor for stroke. But exact mechanisms behind this correlation are unknown and remain to be investigated. To understand underlying mechanisms of stroke on AD pathophysiology and sex-specific differences, we investigated the effect of ischemic stroke on female and male double transgenic APPSWE/PS1ΔE9 (AD) and C57BI/6 wild type (WT) mice from 3- months until 12- months of age. Mice were subjected to transient occlusion of the right middle cerebral artery (tMCAo) to induce an ischemic stroke. Before the stroke induction baseline measurement of general health parameters (e.g, body weight, blood pressure) and motor skills (e.g. activity, strength, coordination) were measured. After stroke induction, these measurements were repeated at several time points along with MRI measurements (e,g, rsfMRI, DTI, FAIR-ASL) to assess the effect of stroke on brain structure, function, and connectivity. APPSWE/PS1ΔE9 mice and stroke mice showed impairments in physiological parameters, motor function, locomotion, and cognition. Our data show that stroke not only contributes significantly to AD but also exarcerbates the symptoms. APPSWE/PS1ΔE9 stroke mice were more hyperactive and anxious than APPSWE/PS1ΔE9 sham mice. Furthermore, male mice showed greater surgery effects than female mice, indicating strong sex differences in stroke and AD pathophysiology. Our findings suggest that there is a strong correlation between vascular risk factors, stroke and AD. We further showed that there is a great difference between sexes and genotypes, indicating any preventative or therapeutic approach should be personalized.
Description
Citation
Supervisor
Faculty
Faculteit der Sociale Wetenschappen