Age is a major risk factor for developing Alzheimer’s disease (AD). Imaging and biomarker data suggests that the pathophysiological processes of AD begin more than a decade prior to the diagnosis of dementia. Using positron emission tomography (PET), amyloid beta (Aß) plaques and tau tangles have been extensively imaged and used to predict the risk for developing AD. Nonetheless, emerging evidence shows that cerebral metabolic and vascular deficits occur decades before the aggregation of Aß and tau. Specifically, young, cognitively normal individuals who are at high risk for AD (e.g., APOE4 carriers or those with family history of AD) already show significantly reduced cerebral metabolic rates of glucose (CMRglc), cerebral metabolic rate of oxygen (CMRO2), and cerebral blood follow (CBF). Failure to maintain CMRglc leads to synaptic dysfunction; impaired CMRO2 increases oxidative stress and mitochondrial dysfunction; and reduced CBF links to anxiety, depression, and impaired blood-brain barrier (BBB) integrity. These metabolic and vascular deficits precede brain structural alteration (grey matter and white matter atrophy), and ultimately lead to cognitive impairment and dementia.
For the early detection of the potential risk for developing AD, it is imperative to understand and differentiate metabolic and vascular changes between cognitive aging and AD. Neuroimaging methods have been developed as powerful biomarkers for identifying in vivo metabolic and vascular functions. For example, CMRglc and CMRO2 can be determined by PET, and CBF can be measured by both PET and magnetic resonance imaging (MRI). Multi-nuclei magnetic resonance spectroscopy (MRS) can be used to measure bioenergetics in vivo, including oxygen-17 for CMRO2, phosphorus-31 for adenosine triphosphate (ATP), and carbon-13 for for mitochondria oxidative metabolism and neuronal activity. In addition, confocal or multi-photon microscopic imaging have been used to determine BBB integrity and cerebral microinfarcts. All of these state-of-the-art neuroimaging technologies have been applied to study brain aging and AD.
In this Research Topic, we welcome contributions to address the critical needs for developing metabolic and vascular neuroimaging biomarkers for brain aging and AD. We welcome both preclinical and clinical studies with imaging technology including, but not limited to, PET, MRI, MRS, and microscopic imaging. We believe that this series of publications will stimulate conversation and discussion toward the potential prevention of AD, slowing brain aging by protecting metabolic and vascular functions with age, and the potential of using neuroimaging as surrogate markers for the design and determination of effective interventions.
Age is a major risk factor for developing Alzheimer’s disease (AD). Imaging and biomarker data suggests that the pathophysiological processes of AD begin more than a decade prior to the diagnosis of dementia. Using positron emission tomography (PET), amyloid beta (Aß) plaques and tau tangles have been extensively imaged and used to predict the risk for developing AD. Nonetheless, emerging evidence shows that cerebral metabolic and vascular deficits occur decades before the aggregation of Aß and tau. Specifically, young, cognitively normal individuals who are at high risk for AD (e.g., APOE4 carriers or those with family history of AD) already show significantly reduced cerebral metabolic rates of glucose (CMRglc), cerebral metabolic rate of oxygen (CMRO2), and cerebral blood follow (CBF). Failure to maintain CMRglc leads to synaptic dysfunction; impaired CMRO2 increases oxidative stress and mitochondrial dysfunction; and reduced CBF links to anxiety, depression, and impaired blood-brain barrier (BBB) integrity. These metabolic and vascular deficits precede brain structural alteration (grey matter and white matter atrophy), and ultimately lead to cognitive impairment and dementia.
For the early detection of the potential risk for developing AD, it is imperative to understand and differentiate metabolic and vascular changes between cognitive aging and AD. Neuroimaging methods have been developed as powerful biomarkers for identifying in vivo metabolic and vascular functions. For example, CMRglc and CMRO2 can be determined by PET, and CBF can be measured by both PET and magnetic resonance imaging (MRI). Multi-nuclei magnetic resonance spectroscopy (MRS) can be used to measure bioenergetics in vivo, including oxygen-17 for CMRO2, phosphorus-31 for adenosine triphosphate (ATP), and carbon-13 for for mitochondria oxidative metabolism and neuronal activity. In addition, confocal or multi-photon microscopic imaging have been used to determine BBB integrity and cerebral microinfarcts. All of these state-of-the-art neuroimaging technologies have been applied to study brain aging and AD.
In this Research Topic, we welcome contributions to address the critical needs for developing metabolic and vascular neuroimaging biomarkers for brain aging and AD. We welcome both preclinical and clinical studies with imaging technology including, but not limited to, PET, MRI, MRS, and microscopic imaging. We believe that this series of publications will stimulate conversation and discussion toward the potential prevention of AD, slowing brain aging by protecting metabolic and vascular functions with age, and the potential of using neuroimaging as surrogate markers for the design and determination of effective interventions.
