A5060797786- Neurological Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- Anesthesia and Neurotoxicity Research
- Neurological Disorders and Treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- Dementia and Cognitive Impairment Research
- Nitric Oxide and Endothelin Effects
- Optical Imaging and Spectroscopy Techniques
- Barrier Structure and Function Studies
- Intracerebral and Subarachnoid Hemorrhage Research
- Neuroscience and Neuropharmacology Research
The University of Texas Health Science Center at San Antonio
2018-2023
Longevity Biotech (United States)
2023
Institute for Neurodegenerative Disorders
2019-2021
The University of Texas Health Science Center at Houston
2019
Abstract Vascular mechanisms of Alzheimer’s disease (AD) may constitute a therapeutically addressable biological pathway underlying dementia. We previously demonstrated that soluble pathogenic forms tau (tau oligomers) accumulate in brain microvasculature AD and other tauopathies, including prominently microvascular endothelial cells. Here we show accumulates cells P301S(PS19) mice modeling tauopathy drives AD-like deficits. Microvascular impairments were partially negated by selective...
Abstract Cerebrovascular dysfunction and cognitive decline are highly prevalent in aging, but the mechanisms underlying these impairments unclear. Cerebral blood flow decreases with aging is one of earliest events pathogenesis Alzheimer's disease (AD). We have previously shown that mechanistic/mammalian target rapamycin (mTOR) drives progression mouse models AD impairment associated atherosclerosis, closely recapitulating vascular impairment. In present studies, we sought to determine...
Vascular dysfunction is a universal feature of aging and decreased cerebral blood flow has been identified as an early event in the pathogenesis Alzheimer's disease (AD). Cerebrovascular AD includes deficits neurovascular coupling (NVC), mechanism that ensures rapid delivery energy substrates to active neurons through supply. The mechanisms underlying NVC impairment AD, however, are not well understood. We have previously shown mechanistic/mammalian target rapamycin (mTOR) drives...
Abstract Cerebral amyloid angiopathy (CAA) is characterized by fibrillar β (Aβ) association with cerebrovasculature, which leads to impaired brain vascular function, and present in 87% of people Alzheimer’s disease (AD). We previously showed that inhibition mTOR rapamycin prevented BBB breakdown reduced Aβ 18-19 month old Tg2576 mice model AD-associated CAA. This finding suggests attenuation restores integrity the blood barrier (BBB) concomitantly reduces accumulation this mouse model....
Abstract Background Vascular mechanisms of Alzheimer’s disease (AD) may constitute the most therapeutically addressable biological pathway underlying dementia. Soluble pathogenic forms tau (tau oligomers) accumulate in brain microvasculature AD and other tauopathies, particularly microvascular endothelial cells. Methods Primary human cells (HBEC) were exposed to oligomers. Microtubule stability, eNOS activation, markers senescence measured. Mice expressing P301S‐mutant (P301S(PS19) mice), a...
Cerebrovascular dysfunction emerges prior to the onset of cognitive in Alzheimer's disease (AD)1. Specifically, patients with AD exhibit deficits neurovascular coupling (NVC, increased cerebral blood flow evoked by neuronal activation), which is recapitulated various mouse models AD. We have previously identified mammalian/mechanistic target rapamycin (mTOR) as a major driver brain vascular AD2. Therefore, aims present study were 1) establish mTOR-dependent contribution NVC mice, and 2)...
Our laboratory recently reported the accumulation of pathogenic soluble aggregated tau (tau oligomers) in cerebral microvasculature human patients with tauopathies, including Alzheimer's disease (AD). The functional consequences cerebrovascular accumulation, however, are not yet understood. aim present study was to determine whether brain microvascular leads dysfunction. To this end, we assessed coupling between increased neural activity and blood flow, a highly regulated processes called...
Tau is a microtubule stabilizing protein. When tau becomes hyperphosphorylated, it disassociates from microtubules and forms oligomers which can further aggregate into neurofibrillary tangles. It has been proposed that misfolded species propagate between neurons in prion-like fashion, causing the aggregation of native target cell. In addition to also shown soluble are present brain vasculature Alzheimer's disease patients. Primary human microvascular endothelial cells (HBECs) were cultured...