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2021 Annual Report

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This is the 2021 Annual Report for Van Andel Institute.

Department of

Department of Neurodegenerative Science The Institute’s Department of Neurodegenerative Science is home to experts in Parkinson’s disease and other progressive neurological disorders such as Alzheimer’s and related dementias, and depression. Our goal is to improve quality of life for patients by: Impeding disease progression: VAI scientists are working to better understand the complex causes of Parkinson’s in order to develop new treatments that slow or stop the disease’s progression or even prevent it altogether — something no current treatment can do. Developing ways to repair the brain: The symptoms of Parkinson’s and other neurodegenerative diseases occur when certain brain cells are damaged or killed. At the Institute, scientists are exploring innovative ways to repair this damage and restore lost function. Designing more definitive diagnostic methods: There are currently no definitive diagnostic tests for Parkinson’s, which complicates treatment decisions and puts an undue burden on people with the disease. Institute scientists are searching for biological indicators called biomarkers, which can be assessed objectively and used to improve diagnosis. Investigating the underpinnings of Alzheimer’s and other disorders: VAI’s research extends beyond Parkinson’s into diseases like Alzheimer’s, frontotemporal dementia, amyotrophic lateral sclerosis, and depression and suicidality. 2021 HIGHLIGHTS Blood markers can predict depression in pregnancy (Dr. Lena Brundin) — Signs of inflammation in the blood reliably predict and identify severe depression in pregnancy, reported a study led by Van Andel Institute’s Dr. Lena Brundin and Pine Rest Christian Mental Health Services’ Dr. Eric Achtyes. The team’s analysis established a set of 15 biological markers found in the blood that can predict if pregnant women will experience significant depressive symptoms with more than 80% accuracy. The findings could give physicians a much-needed tool to identify women who may be at risk for depression and better tailor their care throughout pregnancy. 1 Insights into a gene implicated in inherited Parkinson’s may shed light on the disease’s broader underpinnings (Dr. Darren Moore) — Although we don’t yet know exactly what causes more than 90% of Parkinson’s disease cases, the insights gleaned from the remaining 10% may help us better understand — and one day better treat — all types of the disease. This small subset of cases is caused by changes in certain genes that are passed down through families. Now, Dr. Darren Moore and his team have found that one of these genes, VPS35, is a key player in the maintenance and survival of brain cells that regulate movement. They also discovered that problems with this gene appear to interfere with cellular housekeeping, allowing clumps of sticky proteins to form that damage brain cells. Their findings have implications not only for Parkinson’s but also for diseases like amyotrophic lateral sclerosis (ALS). 2 ‘Roadmaps’ of the brain reveal regions vulnerable to Alzheimer’s disease (Dr. Michael Henderson) — Much like a supply truck crossing the countryside, the misfolded proteins that damage neurons in Alzheimer’s disease travel the “roads” of the brain, sometimes stopping or even re-routing to avoid roadblocks, reports a study by VAI’s Dr. Michael Henderson and collaborators at University of Pennsylvania. Understanding how and why this happens could clear the way for the development of new therapies to slow or stop disease progression. 3 Van Andel Institute scientists and collaborators receive more than million in grants to accelerate Parkinson’s disease research (Dr. Michael Henderson and Dr. Hong-yuan Chu) — Two VAI scientists and their collaborators were awarded more than million to advance Parkinson’s disease research and accelerate development of new therapies. This pair of awards, called Collaborative Research Network grants, comes from Aligning Science Across Parkinson’s, a coordinated research initiative to accelerate the pace of discovery and inform the path to a cure for Parkinson’s through collaboration, research-enabling resources and data sharing. 8

RESEARCH VAI’s Dr. Michael Henderson and colleagues at Yale University and University of Pennsylvania were awarded million to identify areas and cell types in the brain that may be particularly vulnerable to Parkinson’s disease. 4 VAI’s Dr. Hong-yuan Chu and colleagues at Emory University were awarded .3 million to investigate the brain’s motor cortex — which helps manage movement — and its role in Parkinson’s. Changes to the cells that comprise this critical brain region have long been implicated in the disease. They also will collaborate with scientists at SUNY Downstate and INSCOPIX. 5 Understanding gut inflammation may hold clues to mitigating Parkinson’s onset (Dr. Patrik Brundin) — Chronic inflammation in the gut may propel processes in the body that give rise to Parkinson’s disease, according to a study by Dr. Patrik Brundin’s lab at VAI and colleagues at Roche. The findings add to a growing list that links the gut and the immune system to Parkinson’s, and track with several large-scale studies that show an association between Parkinson’s and inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease. 6 Funding Acknowledgements Research reported in this publication was supported by: 1 Van Andel Institute, Pine Rest Christian Mental Health Services and the National Institute of Mental Health of the National Institutes of Health under award no. R01MH104622 (Brundin). The clinical trial identifier is NCT02566980. 2 National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award nos. R01NS105432 (Moore), R01NS117137 (Moore) and R01NS101958 (Cowell); American Parkinson Disease Association (Sargent); and Van Andel Institute. 3 The Michael J. Fox Foundation for Parkinson’s Research award no. 16879 (Henderson); the National Institute on Aging of the National Institutes of Health under award nos. T32AG000255 (Lee), P30AG010124 (Trojanowski) and U19AG062418 (Trojanowski); the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award nos. P50-NS053488 (Trojanowski) and R01NS099348 (Bassett); the National Institute of Mental Health of the National Institutes of Health under award no. F30MH118871-01 (Cornblath); and the National Science Foundation under award nos. PHY1554488 (Bassett) and BCS1631550 (to Bassett). Bassett also acknowledges support from the John D. and Catherine T. MacArthur Foundation, the ISI Foundation, the Alfred P. Sloan Foundation, and the Paul G. Allen Foundation. 4 Funds from Yale University as part of an Aligning Science Across Parkinson’s Collaborative Research Network award. 5 Funds from Emory University as part of an Aligning Science Across Parkinson’s Collaborative Research Network award. 6 Van Andel Institute and Roche. Early work on this project was supported in part by the European Research Council. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other granting organizations. 9

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