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eBriefing

New Developments in Alzheimer’s Disease Therapeutics

New Developments in Alzheimer’s Disease Therapeutics
Reported by
Sara Donnelly

Posted March 05, 2021

Presented By

The Brain and Behavior Discussion Group

The New York Academy of Sciences

The prevalence of Alzheimer’s disease (AD) is increasing in the US and worldwide. Currently, more than five million people in the US suffer from AD, and this number is projected to more than double by 2050. Despite this, there are no approved disease-modifying therapeutics for this devastating neurodegenerative disorder. Although amyloid pathology is a hallmark of AD, recent clinical trials targeting amyloid have yielded disappointing results leading to increased efforts to identify new disease drivers and alternative drug targets. Moreover, there is a great need for improved tools to detect AD in its earliest stages, when therapies are likely to be most effective. This eBriefing features the latest research on topics including neuroinflammation, early detection and diagnostics, sex differences and lifestyle factors, and highlights promising avenues for therapeutic development in AD.


Highlights

  • Sex differences may impact neurodegeneration and the development of Alzheimer's disease. >
  • Digital tools and new blood biomarkers are revolutionizing how Alzheimer's is diagnosed and monitored. >
  • A new therapeutic approach targeting the endoplasmic reticulum and mitochondria shows clinical promise for neurodegenerative diseases. >
  • Medical records and artificial intelligence could be used to predict which patients will develop dementia. >

Speakers

Richard Isaacson
Richard Isaacson, MD

Weill Cornell Medical College

Katerina Akassoglou
Katerina Akassoglu, PhD

Gladstone Institutes

Beth Stevens, PhD
Beth Stevens, PhD

Harvard Medical School

Henrik Zetterberg
Henrik Zetterberg, MD

University of Gothenburg

Jeffrey Kaye
Jeffrey Kaye, PhD

Oregon Health & Sciences University

Maria Teresa Ferretti
Maria Teresa Ferretti, PhD

Women’s Brain Project

Lisa Mosconi
Lisa Mosconi, PhD

Weill Cornell Medical College

Joshua Cohen
Joshua Cohen

Amylyx

Justin Klee
Justin Klee

Amylyx

Thomas McCoy, PhD
Thomas McCoy, PhD

Massachusetts General Hospital, Harvard Medical School

Lifestyle Interventions for Alzheimer's Disease

Speakers

Richard Isaacson, MD
Weill Cornell Medical College 

Richard S. Isaacson, M.D. serves as Director of the Alzheimer’s Prevention Clinic (APC), Weill Cornell Memory Disorders Program, Assistant Dean of Faculty Development, and Associate Professor of Neurology at Weill Cornell Medicine & NewYork-Presbyterian. He completed his residency in Neurology at Beth Israel Deaconess Medical Center/Harvard Medical School, and his medical internship at Mount Sinai Medical Center in Miami Beach, FL. A graduate of the accelerated 6-year B.A./M.D. program at the University of Missouri - Kansas City School of Medicine, Dr. Isaacson now specializes in AD risk reduction and treatment, mild cognitive impairment due to AD and pre-clinical AD. His clinical research has shown that individualized

clinical management of patients at risk for AD dementia may be an important strategy for optimizing cognitive function and reducing dementia risk. He has also led the development of Alzheimer’s Universe (AlzU.org), a vast online education research portal on AD with over 2 million unique visitors since 2014. Leading both clinical research and technology teams, the APC has studied digital biomarkers using a wearable biosensor, and is committed to rigorously evaluating the effects of personalized, evidence-based multi-modal interventions on cognition, serum/radiologic biomarkers of AD and calculated AD and cardiovascular risk.

Richard Isaacson (Weill Cornell Medical College)

Lisa Mosconi, PhD
Weill Cornell Medical College

Dr. Lisa Mosconi, PhD, is Associate Professor of Neuroscience in Neurology and Radiology at Weill Cornell Medical College, where she serves as Director of the Women’s Brain Initiative and Associate Director of the Alzheimer’s Prevention Clinic. She also is an adjunct faculty member at the Department of Psychiatry at NYU School of Medicine.

Dr. Mosconi holds a dual PhD degree in Neuroscience and Nuclear Medicine. She is well known for her research on the early detection of Alzheimer’s disease in at-risk individuals, especially women, using brain imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI). Dr. Mosconi’s work is focused on how risk of memory loss and Alzheimer’s disease can be minimized through the combination of appropriate medical care and lifestyle modifications.
She is the author of New York Times bestselling “THE XX BRAIN: The Groundbreaking

Lisa Mosconi (Weill Cornell Medical College)

Maria Teresa Ferretti, PhD
Women’s Brain Project

 

Maria Teresa is a neuroimmunologist and science advocate with over 10-year international experience in the field of Alzheimer’s disease, and a unique expertise on sex and gender differences.

After a master in Pharmaceutical Chemistry in 2005 (University of Cagliari, Italy) and a stage at the Center of Excellence for Drug Discovery of GlaxoSmith&Kline (Harlow, England), she obtained a PhD in Pharmacology and Therapeutics at McGill University (Montreal, Canada) in 2011 with a thesis on the role of inflammation in Alzheimer’s Disease with dr Claudio Cuello.

In 2011 she moved back to Europe and joined the Nitsch’s lab (University of Zurich, Switzerland) as postdoc and group leader, to further study the role of the immune system in Alzheimer’s. During this time, she performed deep immunophenotyping of animal models of Alzheimer’s and established in the lab the first protocols for multidimensional characterization of human blood cells using mass cytometry.

In 2016 Maria Teresa co-founded the non-profit organization called ‘Women’s Brain Project’ (WBP, CHE-369.271.906). The non-profit studies sex- and gender-sensitive precision medicine for brain and mental diseases such as Alzheimer, migraine, multiple sclerosis, depression etc (www.womensbrainproject.com). Maria Teresa currently serves as the Chief Scientific Officer of the organization; she is also an external teacher at the Medical University of Vienna. Austria.

Her work as WBP Chief Scientific Officer has led to several scientific publications in leading journals including Nature, Science and PNAS, three TED-x talks (https://youtu.be/9nWpkv0o55U), and coverage by both the national (Sonntagszeitung, SwissInfo, NZZ, Le Temps) and the international press (including BBC, The Independent, Sciences et Avenir, Financial Times, La Stampa, ELLE Italy). As WBP Chief Scientific Officer she is a sought-after speaker, and gives regular talks, lectures and presentation, both at scientific and lay public meetings. She is a Faculty member of the Course for Advance studies (CAS) on gender medicine at University of Zurich (Switzerland) and the editor of the book ‘Sex differences in Alzheimer’s Disease’ published by Elsevier.

Maria Teresa Ferretti (Women’s Brain Project)

Further Readings

Isaacson

Berkowitz CL, Mosconi L, Scheyer O, Rahman A, et al.

Healthcare (Basel). 2018 Jul 13;6(3):82.

Isaacson RS, Hristov H, Saif N, et al.

Alzheimers Dement. 2019 Dec;15(12):1588-1602.

Mosconi

Rahman A, Schelbaum E, Hoffman K, et al.

Neurology. 2020 Jul 14;95(2):e166-e178.

Scheyer O, Rahman A, Hristov H, et al.

J Prev Alzheimers Dis. 2018;5(4):225-230.

Biomarkers and Digital Health

Speakers

Henrik Zetterberg, MD
University of Gothenburg

Henrik Zetterberg is a Professor of Neurochemistry at the University of Gothenburg, Sweden, and University College London, UK, and a Clinical Chemist at Sahlgrenska University Hospital in Gothenburg, Sweden. He is Head of the Department of Psychiatry and Neurochemistry at the University of Gothenburg and leads the UK DRI Fluid Biomarker Laboratory at UCL. His main research focus and clinical interest are fluid biomarkers for brain diseases, Alzheimer’s disease in particular. He has published more than 1300 scientific articles and received numerous awards.

Henrik Zetterberg (University of Gothenburg)

Jeffrey Kaye, PhD
Oregon Health & Sciences University

Dr. Kaye is the Layton Professor of Neurology and Biomedical Engineering at Oregon Health and Science University (OHSU). He directs ORCATECH (the Oregon Center for Aging and Technology), the affiliated ORCASTRAIT (Oregon Roybal Center for Care Support Translational Research Advantaged by Integrating Technology), and the NIA - Layton Aging and Alzheimer’s Disease Research Center at OHSU. His research has focused on factors promoting health and function into advanced age, while developing and testing interventions to maintain wellbeing by advancing the science of meaningful clinical assessment. He leads or has led several longitudinal studies on aging and clinical trials including: the Intelligent Systems for Detection of Aging Changes (ISAAC), the ORCATECH Life Laboratory, the Ambient Independence Measures for Guiding Care Transitions, and the Collaborative Aging Research using Technology (CART) Initiative studies, all using digital technologies for assessment and developing interventions directed toward transitions signaling imminent health and functional change. He is listed in Best Doctors in America. He serves on many national and international panels and boards in the fields of geriatrics, neurology, and technology. He is an author of over 400 scientific publications and holds several major grant awards from federal agencies, national foundations, and industrial sponsors.

Jeffrey Kaye (Oregon Health & Sciences University)

Further Readings

Targeting Neuroinflammation and Energy Dysfunction

Speakers

Beth Stevens, PhD
Harvard Medical School

Beth Stevens received her PhD in Neuroscience in 2003 from the University of Maryland, College Park, and completed her postdoctoral fellowship at the Stanford University School of Medicine in 2008. She is a recipient of the 2008 Smith Family Award for Excellence in Biomedical Research, a 2010 Dana Foundation Award (Brain and Immunoimaging), and a 2010 Ellison Medical Foundation New Scholar in Aging award. Dr. Stevens received the Presidential Early Career Award for Scientists and Engineers in 2012. In 2015, she was selected for a MacArthur Foundation Fellowship.

The Stevens laboratory is interested in interactions between the two fundamental cell types of the nervous system, neurons and glia. Research seeks to understand how neuron-glia communication facilitates the formation, elimination, and plasticity of synapses—the points of communication between neurons—during both healthy development and disease.

Beth Stevens (Harvard Medical School)

Justin Klee & Joshua Cohen
Amylyx

Justin Klee and Joshua Cohen co-founded Amylyx Pharmaceuticals in 2013, while still undergraduates at Brown University, and serve as co-CEOs. From their dorm rooms to today, Justin and Josh oversaw the development of an investigational therapy for ALS and Alzheimer’s Disease by working with top hospitals and investigators around the country, raising over $75,000,000 in funding and overseeing all preclinical, regulatory and clinical operations and strategy to bring AMX0035 through clinical trials. Josh and Justin have built a team of industry leaders rapidly growing the company to team of 21 full time employees. In 2020, the company published the CENTAUR trial which showed a significant slowing in ALS disease progression compared to placebo, providing hope and a potential new therapy for people with ALS. Justin and Josh have both advocated for ALS patients in meetings in the US House of Representatives and Senate. Justin previously did research at Brown University in neural systems and neurophysiology and Alzheimer’s disease at Harvard Medical School and received his Sc.B in Neuroscience from Brown University, while Josh’s research experience includes work both at Brown University and at the National Institute of Standards in Technology. Josh received his BSE in biomedical engineering from Brown University. In 2019, Josh and Justin won Xconomy’s Young Innovator Award and in 2020 were named to Business Insider’s 30 under 40 in health care list and PM360’s Elite in the Drug Researchers and Developers Category. Amylyx was also recently selected as one of Fierce Biotech’s 2020 Fierce 15 companies.

Justin Klee/Joshua Cohen (Amylyx)

Further Readings

Stevens

Wilton DK, Dissing-Olesen L, Stevens B.

Annu Rev Neurosci. 2019 Jul 8;42:107-127.

Cohen/Klee

Paganoni S, Macklin EA, Hendrix S, et al

N Engl J Med. 2020 Sep 3;383(10):919-930.

Predicting Dementia with AI

Speakers

Thomas McCoy, PhD
Massachusetts General Hospital, Harvard Medical School


Dr. McCoy is the Director of Research at the Massachusetts General Hospital Center for Quantitative Health. His work focuses on applications of methods drawn from computer science, most recently natural language processing and machine learning, to electronic health record data. His current subject areas of interest are multidimensional psychiatric phenotypes and biologically informed models of medication effects for repositioning and adverse event prediction. Dr. McCoy is a graduate of Dartmouth College, Cornell Medical College, and The MGH / McLean adult psychiatry residency where he served CL chief resident and research fellow in the Center for Experimental Drugs and Diagnostics. He is a practicing psychiatrist with a clinical interest in medical ethics, end of life, neurodegeneration and delirium

Thomas McCoy (Massachusetts General Hospital, Harvard Medical School)

Further Readings

McCoy

McCoy TH Jr, Han L, Pellegrini AM, et al.

Alzheimers Dement. 2020 Mar;16(3):531-540.

Hart KL, Pellegrini AM, Forester BP, et al.

Gen Hosp Psychiatry. 2020 Nov 10;68:46-51.