{"id":1344,"date":"2016-10-21T14:18:17","date_gmt":"2016-10-21T21:18:17","guid":{"rendered":"https:\/\/keck.usc.edu\/news\/zlokovic-receives-nearly-25-million-to-study-alzheimers-disease\/"},"modified":"2023-11-19T12:16:22","modified_gmt":"2023-11-19T20:16:22","slug":"zlokovic-receives-nearly-25-million-to-study-alzheimers-disease","status":"publish","type":"post","link":"https:\/\/keck.usc.edu\/news\/zlokovic-receives-nearly-25-million-to-study-alzheimers-disease\/","title":{"rendered":"Zlokovic receives nearly $25 million to study Alzheimer\u2019s disease"},"content":{"rendered":"\n \n \n\n\n\n\n\n\n\n
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\n\n \n Press Release<\/span>\n\n\n\n<\/div>\n \n \n
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Zlokovic receives nearly $25 million to study Alzheimer\u2019s disease<\/h1>\n\n\n<\/div>\n \n \n
\n \u00a0Zen Vuong<\/span>\n \n October 21, 2016<\/span>\n <\/div>\n \n \n
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A snapshot of the blood-brain barrier, a gatekeeper that prevents toxic substances from entering the brain.<\/figcaption>\n <\/figure>\n \n \n \n\n<\/div>\n \n\n <\/div><\/div>\n\r\n\r\n\n\n \n \n\n\n\n\n\n\n\n
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Berislav Zlokovic, MD, PhD<\/a>, a pioneer of the theory that fixing the brain\u2019s leaky blood vessels will prevent Alzheimer\u2019s disease, has received four grants totaling up to $24.9 million over five years.
\nThe funding allows Zlokovic, director of the Zilkha Neurogenetic Institute<\/a>, to attack from different fronts the blood-brain barrier, a gatekeeper that prevents toxic substances from entering the brain.
\n\u201cThe brain contains 400 miles of blood vessels that can stretch from Los Angeles to San Francisco,\u201d said Zlokovic, chair and professor of physiology and biophysics<\/a> at the Keck School of Medicine of USC. \u201cIf there is a leak along this vascular tube and the pothole is, for example, near the hippocampus \u2014 the center of learning and memory \u2014 that can contribute to the development of dementia and Alzheimer\u2019s disease. We can delay the onset or slow the progression of Alzheimer\u2019s if we are able to fix leaky capillaries when they first start, some 10 to 15 years before Alzheimer\u2019s symptoms even surface.\u201d
\nThe National Institute on Aging in the National Institutes of Health awarded Zlokovic and Arthur Toga, PhD, director of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute, $12.3 million. NIH\u2019s National Institute of Neurological Disorders and Stroke presented Zlokovic with $3.6 million. The Alzheimer\u2019s Association will give Zlokovic and Toga up to $3 million, and the Foundation Leducq in Paris asked Zlokovic to be the North American coordinator of a multi-institutional transatlantic program, supporting his work with up to $6 million.
\n\u201cBerislav Zlokovic is a very creative scientist who forges partnerships across disciplines, paving the way for innovation in varied areas ranging from basic Alzheimer\u2019s research to clinical trials,\u201d said Rohit Varma, MD, MPH<\/a>, interim dean of the Keck School of Medicine and director of the USC Gayle and Edward Roski Eye Institute. \u201cHe is an internationally renowned clinician-scientist recognized for his contributions to age-related changes and diseases of the brain. Dr. Zlokovic\u2019s work has the potential to help millions of people who have or may develop Alzheimer\u2019s disease.\u201d
\nMore than 5 million Americans currently live with Alzheimer\u2019s, a disease that kills more people than breast and prostate cancer combined, according to the Alzheimer\u2019s Association. Alzheimer\u2019s is the sixth leading cause of death in the United States.
\nUSC researchers in multiple disciplines are seeking to untangle intractable diseases and conditions attached to aging, including Alzheimer\u2019s and dementia.
\nMany Alzheimer\u2019s disease researchers focus on the tangles of tau proteins in the brain or beta-amyloid plaque that may block cell-to-cell signaling at synapses. Zlokovic, however, believes vascular dysfunction predates and contributes to these manifestations.
\n\u201cThe blood-brain barrier\u2019s leaks allow many blood-derived toxic products, cells and pathogens to enter the brain and directly damage brain circuits involved in memory and learning,\u201d Zlokovic said. \u201cAdditionally, bad proteins that normally are ejected from the brain, such as beta-amyloid, have to struggle against the flow of traffic. This situation can eventually lead to \u2018a second hit\u2019: Beta-amyloids and tau tangles remain in the brain and cause damage that become evident years later.\u201d
\nThe following points detail Zlokovic\u2019s four new research projects:
\nZlokovic and Toga will advance current knowledge on the contributions of blood vessels to dementia and Alzheimer\u2019s disease. They will study humans with genetic risk of Alzheimer\u2019s and use a rat model of Alzheimer\u2019s disease to establish whether the brain\u2019s vascular system plays a major role in the onset and progression of cognitive impairment. Additionally, they will develop new molecular and imaging biomarkers of the disease.
\nThey also will test whether 3K3A-APC, a neuroprotective enzyme developed by Zlokovic\u2019s team that is in Phase II clinical trials among stroke patients, can stabilize the vascular system in rats with Alzheimer\u2019s. That would theoretically delay disease onset and slow the development of amyloid and tau pathology.
\nThis multi-institutional study will also include the Huntington Medical Research Institutes, Washington University in St. Louis, the Banner Alzheimer\u2019s Institute and Mayo Clinic.
\n\u201cWe are confident that the proposed studies will have a significant impact on our understanding of the development of pathology, treatment and early prevention of dementia and Alzheimer\u2019s disease,\u201d Zlokovic said.
\nUp to 45 percent of all dementias worldwide are wholly or partly due to age-related small vessel disease of the brain, Zlokovic said. His team will study the role of pericytes, the sentinels stationed at exclusive doorways into and out of the blood-brain barrier.
\nHis team will examine how pericyte loss in a mouse model leads to blood-brain barrier breakdown, cerebral blood flow reductions, damage to the brain\u2019s circuitry and neuron loss. They hope to establish perictye as a new key target for white matter disease, the age-related wearing away of tissue in the largest and deepest part of the brain.
\nZlokovic and Toga will use novel imaging techniques to examine the molecular biomarkers of the brain\u2019s vascular integrity. They will follow human participants with no cognitive impairment and ones with mild cognitive impairment over four to five years to see how the brain\u2019s blood vessels and cerebral blood flow affect amyloid and tau lesions in apolipoprotein E4 (APOE4) carriers and non-carriers. APOE4 has been implicated in Alzheimer\u2019s disease.
\nZlokovic will lead the Foundation Leducq\u2019s North American Transatlantic Networks of Excellence Program, which will include three North American and four European centers. The team will study the function and pathology of perivascular spaces in the brain, the key compartments that interface between blood vessels and the brain.
\nThe program has two design paths. Under preclinical objectives, researchers will use multiple imaging techniques in different live rodent models experiencing small vessel disease. Under clinical objectives, they will study patients who have stroke or cognitive displays of small vessel disease. They will also use advanced MRI methods to examine patients with sleep apnea who have low-oxygen levels in the brain and disturbed sleep.
\nThe research will determine the structure of the perivascular space, how cerebral brain fluid reacts to changes in brain equilibrium and blood-brain barrier leakage. The ultimate goal is to identify therapeutic targets for the treatment of small vessel disease of the brain, which may contribute to cognitive impairment.<\/p>\n\n\n\n<\/div>\n <\/div>\n\n\n <\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":60,"featured_media":1345,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"advgb_blocks_editor_width":"","advgb_blocks_columns_visual_guide":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[6],"tags":[20,42],"class_list":["post-1344","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-press-release","tag-research","tag-zilkha"],"acf":[],"yoast_head":"\nZlokovic receives nearly $25 million to study Alzheimer\u2019s disease<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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