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Super-resolution imaging of brain microvascular changes in a model of Alzheimer Disease

阿尔茨海默病模型脑微血管变化的超分辨率成像

基本信息

批准号：
10430929
负责人：
DANIEL A LLANO
金额：
$ 42.15万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10430929
关键词：
Aerobic Exercise Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease pathology Alzheimer&apos s disease risk Anatomy Animal Disease Models Animals Area Automobile Driving Autopsy Behavior Biological Blood Blood Vessels Blood Volume Blood capillaries Blood flow Brain Brain Diseases Brain imaging Brain region Cerebrovascular Circulation Cerebrovascular system Chronic Cognition Cognitive Communities Coupled Data Development Diabetes Mellitus Disease Exercise Functional Imaging Goals Hippocampus (Brain)Human Hypertension Illness impact Image Imaging Device Imaging Techniques Impaired cognition Individual Intervention Life Longevity Measures Microscopy Mus Nerve Degeneration Obesity Pathogenesis Penetration Physical Exercise Physiology Population Public Health Research Resolution Rest Risk Factors Science Societies Speed Structure Techniques Therapeutic Intervention Time Tissue imaging Tissues Work abeta deposition age group age related aging population angiogenesis base cardiovascular risk factor cerebral microvasculature cognitive change cognitive function effective therapy high risk histological studies imaging approach imaging study microvascular pathology middle age millimeter mouse model novel novel imaging technique preservation ultrasound vascular risk factor

项目摘要

Project Summary Although biomedical science has made remarkable progress in extending the human lifespan, this lengthening of life has not necessarily been matched by longevity in cognition. Older individuals are at significantly higher risk for developing Alzheimer Disease (AD). Thus, the rising numbers of older individuals, coupled with aging-related risk for AD, is rapidly becoming a public health crisis. It is therefore important that we understand the mechanisms underlying declining cognitive function in AD. Although many mechanisms underlying cognitive decline in AD have been proposed, two universal findings motivate the current work: 1) vascular risk factors are a strong predictor of AD and 2) histopathological studies have shown profound alterations in the microvasculature of the AD brain. Although these studies point to vascular compromise as a potential contributory agent of AD-associated cognitive decline, there are currently no techniques available that permit a detailed assessment of the cerebral microvasculature of deep and superficial blood vessels in a living animal. Thus, it has not been possible to track vascular changes over time or to determine the impact of therapeutic interventions on the cerebral microvasculature. To this end, our team has been developing a novel form of super- resolution vascular imaging known as ultrasound localization microscopy (ULM). ULM can image micron-size blood vessels many millimeters deep into the brain, and can capture dynamics of blood flow (speed, flow uniformity and direction) which are not available using histological studies. Here, we propose to use ULM to investigate AD-related changes in blood flow dynamics and will relate them to AD-related changes in behavior in a mouse model of AD. In addition, we will determine if an intervention known to mitigate AD-related cognitive changes – aerobic exercise – restores regional cerebral microvasculature dynamics in AD model animals. Successful completion of this work will not only unveil previously poorly understood changes in microvascular dynamics with AD, but will also advance a novel imaging technique with broad potential applications to understand many other disorders of the brain.

项目总结