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Principal Investigator: Yongxian Qian
Organization: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
Fiscal Year: 2024
Award: $751,680
Funding agency: National Institute on Aging
ABSTRACT
Disruption of cerebrospinal fluid (CSF) clearance pathway (glymphatic system) might contribute to development
of Alzheimer's disease (AD), which is characterized by excessive deposition of toxic soluble amyloid beta (A-
beta) proteins in the brain. Recent studies of mice demonstrated that impairment of the CSF clearance pathway
led to a 70% reduction in A-beta clearance, while sleep-induced enhancement of CSF flow increased A-beta
clearance by 100%. It is unclear whether or not these impairment and enhancement effects exist in humans and
how they change with aging. Technical limitations of noninvasive approaches hinder adequate study of CSF
clearance in humans. Here we propose two new techniques to determine whether CSF clearance is enhanced
during sleep, degenerated in normal aging, and disrupted in AD. Instead of studying perivascular space, this
project investigates the production (at choroid plexus), bulk flow (in parenchyma), and drainage (at arachnoid
villi) of CSF in the brain simultaneously. The overarching goal is to understand the changes in CSF clearance in
normal aging and in AD. The proposed techniques include 1) dynamic sodium (23Na) MRI that quantifies velocity
of CSF bulk flow in brain parenchyma and 2) ultrashort echo time (UTE) proton (1H) MRI that uses UTE-T2*
value to quantify calcification of choroid plexus and assess deficiency of CSF production and uses high resolution
(0.22 mm) to visualize trabecular structures in arachnoid villi and evaluate resistance of CSF drainage. We aim
to determine: 1) how age affects CSF production, bulk flow, and drainage in the normal brain; 2) the impact of
sleep on CSF clearance in the normal aging brain; and 3) whether CSF clearance is disrupted in AD patients.
This work will generate highly-desired valuable knowledge about the degeneration of CSF clearance in normal
aging and disruption in AD, which will help design and determine effective interventions for and strategies to
prevention of AD development.
Terms: <21+ years old><AD dementia><AD prevention><Abeta clearance><Adult><Adult Human><Affect><Age><Aging><Alzheimer Type Dementia><Alzheimer beta-Protein><Alzheimer disease dementia><Alzheimer disease prevention><Alzheimer prevention><Alzheimer risk factor><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Amyloid beta-Protein><Alzheimer's Disease><Alzheimer's amyloid><Alzheimer's disease patient><Alzheimer's disease risk><Alzheimer's patient><Alzheimers Dementia><Amentia><Amyloid (Aβ) plaques><Amyloid Alzheimer's Dementia Amyloid Protein><Amyloid Beta-Peptide><Amyloid Plaques><Amyloid Protein A4><Amyloid beta-Protein><Amyloid β><Amyloid β clearance><Amyloid β-Peptide><Amyloid β-Protein><Aβ><Aβ clearance><Blood Vessels><Brain><Brain Nervous System><CNS lymphatic system><CSF clearance><Calcified><Cerebrospinal Fluid><Choroid Plexus><Data><Dementia><Deposit><Deposition><Development><Drainage><Drainage procedure><EEG><Early Diagnosis><Electroencephalogram><Electroencephalography><Encephalon><Extracellular Space><Female><Glandulae Pacchioni><Goals><H+ element><Health Care Costs><Health Costs><Healthcare Costs><Human><Hydrogen Ions><Impairment><Individual><Intercellular Space><Knowledge><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Metabolic><Mice><Mice Mammals><Mission><Modern Man><Monitor><Murine><Mus><NIH><NMR Imaging><NMR Tomography><Na element><National Institutes of Health><Neuritic Plaques><Nuclear Magnetic Resonance Imaging><Older Population><Pathway interactions><Primary Senile Degenerative Dementia><Probability><Production><Proteins><Protons><Public Health><Research><Resistance><Resolution><Risk Factors><Senile Plaques><Sleep><Sodium><Structure><Structure of choroid plexus><Study Subject><System><Techniques><Testing><Time><United States><United States National Institutes of Health><Variant><Variation><Visualization><Work><Zeugmatography><a beta peptide><a-beta peptide clearance><abeta><abeta deposition><abeta peptide clearance><adulthood><age associated alterations><age associated changes><age correlated alterations><age correlated changes><age dependent alterations><age dependent changes><age group><age related alterations><age related changes><age specific alterations><age specific changes><aged brain><aged group><aged groups><aged individual><aged individuals><aged people><aged person><aged persons><aged population><aged populations><ages><aging brain><aging population><alterations with age><alzheimer risk><amyloid beta><amyloid beta clearance><amyloid beta deposition><amyloid beta peptide clearance><amyloid beta plaque><amyloid β deposition><amyloid-b plaque><amyloid-b protein><arachnoid villi><awake><aβ deposition><aβ plaques><beta amyloid fibril><brain lymph system><brain lymphatic system><brain parenchyma><burden of disease><burden of illness><calcification><cerebral spinal fluid><cerebrospinal fluid clearance><cerebrospinal fluid flow><changes with age><clinical diagnosis><cored plaque><design><designing><developmental><diffuse plaque><disease burden><early detection><effective intervention><elderly patient><glia lymphatic circuit><glia-lymphatic system><glial lymphatic system><glialymphatic circuit><glialymphatic network><glialymphatic pathway><glialymphatic system><glymphatic clearance pathway><glymphatic pathway><glymphatic system><glymphatic-lymphatic system><glymphatics><insight><male><mid life><mid-life><middle age><middle aged><midlife><natural aging><new technology><normal aging><normative aging><novel technologies><older groups><older individuals><older patient><older person><paravascular system><pathway><patient living with Alzheimer's disease><patient suffering from Alzheimer's disease><patient with Alzheimer's><patient with Alzheimer's disease><population aging><primary degenerative dementia><resistant><resolutions><senile dementia of the Alzheimer type><sex><soluble amyloid precursor protein><spinal fluid><vascular><wasting>