{"id":3170,"date":"2020-04-29T10:14:02","date_gmt":"2020-04-29T17:14:02","guid":{"rendered":"https:\/\/keck.usc.edu\/news\/alzheimers-gene-triggers-early-breakdowns-in-blood-brain-barrier-predicting-cognitive-decline\/"},"modified":"2024-11-07T16:12:37","modified_gmt":"2024-11-08T00:12:37","slug":"alzheimers-gene-triggers-early-breakdowns-in-blood-brain-barrier-predicting-cognitive-decline","status":"publish","type":"post","link":"https:\/\/keck.usc.edu\/news\/alzheimers-gene-triggers-early-breakdowns-in-blood-brain-barrier-predicting-cognitive-decline\/","title":{"rendered":"Alzheimer\u2019s gene triggers early breakdowns in blood-brain barrier, predicting cognitive decline"},"content":{"rendered":"\n \n \n\n\n\n\n\n\n\n
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Alzheimer\u2019s gene triggers early breakdowns in blood-brain barrier, predicting cognitive decline<\/h1>\n\n\n<\/div>\n \n \n
\n \n April 29, 2020<\/span>\n <\/div>\n \n \n
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Damage to pericytes, the layer of cells that wrap around blood vessels in the brain, leads to decline in cognition, and is accelerated in people who carry the APOE4 gene. (Image\/Courtesy of Jim Stanis and Arthur W Toga, Laboratory of Neuro Imaging. USC Stevens Neuroimaging and Informatics Institute, University of Southern California)<\/figcaption>\n <\/figure>\n \n \n \n\n<\/div>\n \n\n <\/div><\/div>\n\n\n\n\n \n \n\n\n\n\n\n\n\n
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New USC research reveals how APOE4 \u2014 a genetic culprit for Alzheimer\u2019s disease \u2014 triggers leaks in the brain\u2019s plumbing system, allowing toxic substances to seep into the brain areas responsible for memory encoding and other cognitive functions.<\/p>\n

The damage is linked to future problems in learning and memory, even when the disease\u2019s signature sticky plaques have not appeared. The findings suggest that the smallest\u00a0blood vessels<\/a>\u00a0in the brain, which form the blood-brain barrier, might be a potential target for early treatment.<\/p>\n

The study appears today in\u00a0Nature<\/a>.<\/p>\n

\u201cThis study sheds light on a new way of looking at this disease and possibly on treatment in people with the APOE4 gene, looking at blood vessels and improving their function to potentially slow down or arrest cognitive decline,\u201d said senior author\u00a0Berislav Zlokovic<\/a>, director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC. \u201cSevere damage to vascular cells called pericytes was linked to more severe cognitive problems in APOE4 carriers. APOE4 seems to speed up the breakdown of the blood-brain barrier by activating an inflammatory pathway in blood vessels, which is associated with pericyte injury.\u201d<\/p>\n

How the APOE4 gene leads to a damaged blood-brain barrier<\/h4>\n

Scientists have long known that the APOE4 gene \u2014 which occurs in up to 14% of the population \u2014\u00a0increases the probability<\/a>\u00a0of developing Alzheimer\u2019s disease. Until now, it\u2019s been unclear how different pathologies determine the course of the disease in its early stages, or what underlying mechanisms lead to cognitive decline in APOE4 carriers.<\/p>\n

\"Berislav<\/a>Zlokovic\u2019s previous research shows that people who develop early memory problems also experience the most leakage in their brain\u2019s blood vessels \u2014 independent of amyloid plaque or tau, two common contributors to Alzheimer\u2019s. The leakage starts when cells called\u00a0pericytes<\/a>, which line the walls of blood vessels in the brain and maintain blood-brain barrier integrity, are damaged. These injured pericytes can be detected with a unique biomarker, developed by\u00a0Zlokovic\u2019s lab<\/a>\u00a0in 2015, which shows up in cerebrospinal fluid.<\/p>\n

For this study, scientists used standard memory tests to check the participants\u2019 cognitive abilities and their neuropsychological performance. They also used advanced neuroimaging and employed the biomarker that indicates damage to the brain\u2019s blood vessels.<\/p>\n

In participants who had the APOE4 gene, researchers found damaged capillaries in the brain\u2019s memory center, the hippocampus and medial temporal lobe. The damage correlated with increased levels of a protein that causes inflammation, cyclophilin A \u2014 an early sign of the disease in people already at higher risk of developing Alzheimer\u2019s.<\/p>\n

Zlokovic, who became director of the Zilkha Neurogenetic Institute in 2012, pioneered the concept that a breakdown in the blood-brain barrier contributes to cognitive impairment and dementia. The Zilkha Neurogenetic Institute opened at Keck School of Medicine in 2003 with a\u00a0$20 million donation\u00a0from Los Angeles businessman Selim Zilkha, who later contributed $10 million more to the effort.<\/p>\n

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In addition to Zlokovic, other authors are Axel Montagne, Daniel A. Nation, Abhay P. Sagare, Giuseppe Barisano, Melanie D. Sweeney, Ararat Chakhoyan, Maricarmen Pachicano, Elizabeth Joe, Amy R. Nelson, Lina M. D\u2019Orazio, John Ringman, Helena C. Chui, Yining Chen, Judy Pa, Meng Law, Peter S. Conti, Arthur W. Toga and Lon Schneider, all of the Keck School of Medicine; David P. Buennagel and Michael G. Harrington of Huntington Medical Research Institutes; Tammie L. S. Benzinger and Anne M. Fagan, John C. Morris of Washington University School of Medicine; Eric M. Reiman of the Banner Alzheimer\u2019s Institute; Richard J. Caselli of the Mayo Clinic; and Julia TCW of the Icahn School of Medicine at Mount Sinai.<\/em><\/p>\n

The study was supported by a combination of grants from the National Institutes of Health, the Alzheimer\u2019s Association, Cure Alzheimer\u2019s Fund, the Foundation Leducq Transatlantic Network of Excellence for the study of Perivascular Spaces in Small Vessel Disease and Open Philanthropy.<\/em><\/p>\n

Additional support is from L.K. Whittier Foundation and National Institute on Aging, the state of Arizona, and from Avid Radiopharmaceuticals Inc., owned by Eli Lilly and Co.<\/em><\/p>\n

\u2014 By Leigh Hopper<\/p>\n\n\n\n<\/div>\n <\/div>\n\n\n <\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":168,"featured_media":3171,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":true,"advgb_blocks_editor_width":"","advgb_blocks_columns_visual_guide":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[6],"tags":[489,34,57,20,632],"class_list":["post-3170","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-press-release","tag-alzheimers-disease","tag-news","tag-recent","tag-research","tag-usc-zilkha-neurogenetic-institute"],"acf":[],"yoast_head":"\nAlzheimer\u2019s gene triggers early breakdowns in blood-brain barrier, predicting cognitive decline<\/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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