Michael S. Rafii, MD, PhD

Professor of Clinical Neurology

Associate Director of ACTC (Alzheimer's Clinical Trial Consortium) and Director of Medical Safety

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Overview

Michael S. Rafii is Medical Director of the Alzheimer’s Therapeutic Research Institute (ATRI) and Professor of Clinical Neurology at the Keck School of Medicine. He obtained his MD and PhD degrees from Brown University and conducted neurogenetics research at Harvard Medical School. He completed his residency in Neurology at the Johns Hopkins Hospital and fellowship in Neurodegenerative diseases at the University of California, San Diego.

Dr. Rafii is a physician-scientist whose research focuses on developing new treatments for Alzheimer’s disease (AD) including a genetic form of AD that occurs in people with Down syndrome (DS). He is Principal Investigator of the NIH-funded Alzheimer’s Clinical Trials Consortium – Down Syndrome (ACTC-DS), where he leads several clinical trials across an international network of academic research sites.

Dr. Rafii also serves as Director of the Medical Safety Unit of the Alzheimer’s Clinical Trials Consortium (ACTC) where he and his team of medical monitors and clinical monitors provide oversight to the safety and conduct of ACTC’s entire portfolio of clinical trials. He is also Co-Director of the Clinical core of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Co-Principal Investigator of the national Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET). Dr. Rafii serves as a scientific reviewer for the NIH and the Alzheimer’s Association. He is author of two of the most widely used review books in neurology: ‘First Aid for the Neurology Boards’ and ‘First Aid for the Neurology Clerkship.’ His work has been featured in the New York Times, Chicago Tribune, Washington Post, Wall Street Journal and National Public Radio (NPR).

Previously, Dr. Rafii served as Medical Director of the Alzheimer’s Disease Cooperative Study, Director of the Memory Disorders Clinic, Founding Director of the Adult Down Syndrome Clinic, Director of the Comprehensive Alzheimer’s Program, Director of the Adult Neurology Residency Training program and Associate Professor of Neurology at the University of California, San Diego.

Awards

  • Alzheimer’s Association : Research Champion Award, 2022
  • LuMind Down Syndrome Research Foundation: David Cox Award, 2016
  • The Johns Hopkins Hospital: Preziosi Outstanding Neurology Resident Award, 2006
  • The Johns Hopkins Hospital: Alpha Omega Alpha, 2006
  • The Johns Hopkins University/Sinai Hospital: Intern of the Year, 2003
  • Brown University School of Medicine: Aronson Prize for Excellence in Neuroscience, 2002

Publications

  • Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid Alzheimers Dement. 2024 Jun 28. . View in PubMed
  • Safety and tolerability of intravenous immunoglobulin infusion in Down syndrome regression disorder Am J Med Genet A. 2024 May; 194(5):e63524. . View in PubMed
  • Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer’s disease: a cross-sectional study Lancet Neurol. 2024 May; 23(5):500-510. . View in PubMed
  • From understanding to action: Exploring molecular connections of Down syndrome to Alzheimer’s disease for targeted therapeutic approach Alzheimers Dement (Amst). 2024 Apr-Jun; 16(2):e12580. . View in PubMed
  • Neuroimaging abnormalities associated with immunotherapy responsiveness in Down syndrome regression disorder Ann Clin Transl Neurol. 2024 Apr; 11(4):1034-1045. . View in PubMed
  • Addressing challenges in health care and research for people with Down syndrome Lancet. 2024 Mar 20. . View in PubMed
  • Plasma Aß42/Aß40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer’s disease Alzheimers Dement. 2024 Feb; 20(2):1214-1224. . View in PubMed
  • Trial of Solanezumab in Preclinical Alzheimer’s Disease N Engl J Med. 2023 Sep 21; 389(12):1096-1107. . View in PubMed
  • Alternative Diagnoses in the Work Up of Down Syndrome Regression Disorder J Autism Dev Disord. 2023 Aug 16. . View in PubMed
  • Safety and tolerability of lumbar puncture for the evaluation of Alzheimer’s disease Alzheimers Dement (Amst). 2023 Apr-Jun; 15(2):e12431. . View in PubMed
  • Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder Res Sq. 2023 Feb 13. . View in PubMed
  • Amyloid-Lowering Monoclonal Antibodies for the Treatment of Early Alzheimer’s Disease CNS Drugs. 2023 08; 37(8):671-677. . View in PubMed
  • Adverse childhood experiences and the development of Down syndrome regression disorder Am J Med Genet A. 2023 07; 191(7):1769-1782. . View in PubMed
  • Detection and treatment of Alzheimer’s disease in its preclinical stage Nat Aging. 2023 05; 3(5):520-531. . View in PubMed
  • The AHEAD 3-45 Study: Design of a prevention trial for Alzheimer’s disease Alzheimers Dement. 2023 04; 19(4):1227-1233. . View in PubMed
  • Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer’s disease: a cross-sectional study Lancet Neurol. 2023 01; 22(1):55-65. . View in PubMed
  • Down Syndrome in a New Era for Alzheimer Disease JAMA. 2023 12 12; 330(22):2157-2158. . View in PubMed
  • Hypovitaminosis D in persons with Down syndrome and autism spectrum disorder J Neurodev Disord. 2023 10 25; 15(1):35. . View in PubMed
  • Immunotherapy responsiveness and risk of relapse in Down syndrome regression disorder Transl Psychiatry. 2023 08 08; 13(1):276. . View in PubMed
  • Editorial: Appropriate Use Recommendations for Lecanemab J Prev Alzheimers Dis. 2023; 10(3):356. . View in PubMed
  • Early-stage Alzheimer disease: getting trial-ready Nat Rev Neurol. 2022 07; 18(7):389-399. . View in PubMed
  • Development of treatments for Down syndrome Lancet Neurol. 2022 01; 21(1):22-23. . View in PubMed
  • Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus Front Neurol. 2022; 13:940175. . View in PubMed
  • Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder J Neurodev Disord. 2022 06 03; 14(1):35. . View in PubMed
  • Safety, Tolerability, and Immunogenicity of the ACI-24 Vaccine in Adults With Down Syndrome: A Phase 1b Randomized Clinical Trial JAMA Neurol. 2022 06 01; 79(6):565-574. . View in PubMed
  • Conducting clinical trials in persons with Down syndrome: summary from the NIH INCLUDE Down syndrome clinical trials readiness working group J Neurodev Disord. 2022 03 23; 14(1):22. . View in PubMed
  • Neurologic complications of Down syndrome: a systematic review J Neurol. 2021 Dec; 268(12):4495-4509. . View in PubMed
  • Alzheimer’s disease associated with Down syndrome: a genetic form of dementia Lancet Neurol. 2021 11; 20(11):930-942. . View in PubMed
  • Feasibility study for detection of retinal amyloid in clinical trials: The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) trial Alzheimers Dement (Amst). 2021; 13(1):e12199. . View in PubMed
  • Integrating Biomarker Outcomes into Clinical Trials for Alzheimer’s Disease in Down Syndrome J Prev Alzheimers Dis. 2021; 8(1):48-51. . View in PubMed
  • Increased Autoimmunity in Individuals With Down Syndrome and Moyamoya Disease Front Neurol. 2021; 12:724969. . View in PubMed
  • Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer’s Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome J Alzheimers Dis. 2021; 79(2):671-681. . View in PubMed
  • Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease: A Truncated Randomized Phase 2b/3 Clinical Trial JAMA Neurol. 2021 03 01; 78(3):293-301. . View in PubMed
  • The search for Alzheimer disease therapeutics – same targets, better trials? Nat Rev Neurol. 2020 11; 16(11):597-598.. View in PubMed
  • Alzheimer’s Disease in Down Syndrome: Progress in the Design and Conduct of Drug Prevention Trials CNS Drugs. 2020 08; 34(8):785-794. . View in PubMed
  • Further understanding the connection between Alzheimer’s disease and Down syndrome Alzheimers Dement. 2020 07; 16(7):1065-1077. . View in PubMed
  • Initiation of symptomatic medication in Alzheimer’s disease clinical trials: Hypothetical versus treatment policy approach Alzheimers Dement. 2020 05; 16(5):797-803. . View in PubMed
  • Diminished Blood Pressure Profiles in Children With Down Syndrome Hypertension. 2020 03; 75(3):819-825. . View in PubMed
  • Down syndrome Nat Rev Dis Primers. 2020 02 06; 6(1):9. . View in PubMed
  • Proteomic profiles for Alzheimer’s disease and mild cognitive impairment among adults with Down syndrome spanning serum and plasma: An Alzheimer’s Biomarker Consortium-Down Syndrome (ABC-DS) study Alzheimers Dement (Amst). 2020; 12(1):e12039. . View in PubMed
  • The AT(N) framework for Alzheimer’s disease in adults with Down syndrome Alzheimers Dement (Amst). 2020; 12(1):e12062. . View in PubMed
  • Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia: A Randomized Clinical Trial JAMA Neurol. 2020 09 01; 77(9):1099-1109. . View in PubMed
  • Effect of AZD0530 on Cerebral Metabolic Decline in Alzheimer Disease: A Randomized Clinical Trial JAMA Neurol. 2019 Oct 01; 76(10):1219-1229. . View in PubMed
  • Predicting the course of Alzheimer’s progression Brain Inform. 2019 Jun 28; 6(1):6. . View in PubMed
  • Tau PET Imaging for Staging of Alzheimer’s Disease in Down Syndrome Dev Neurobiol. 2019 07; 79(7):711-715. . View in PubMed
  • Alzheimer’s Disease Clinical Trials: Moving Toward Successful Prevention CNS Drugs. 2019 02; 33(2):99-106. . View in PubMed
  • Plasma Neurofilament Light and Alzheimer’s Disease Biomarkers in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI) J Alzheimers Dis. 2019; 70(1):131-138. . View in PubMed
  • Prevalence and Severity of Alzheimer Disease in Individuals With Down Syndrome JAMA Neurol. 2019 02 01; 76(2):142-143. . View in PubMed
  • Down syndrome Handb Clin Neurol. 2019; 167:321-336. . View in PubMed
  • Diagnostic biomarkers of Alzheimer’s disease in Down syndrome Lancet Neurol. 2018 10; 17(10):831-832. . View in PubMed
  • Estimating the Evolution of Disease in the Parkinson’s Progression Markers Initiative Neurodegener Dis. 2018; 18(4):173-190. . View in PubMed
  • Bayesian latent time joint mixed-effects model of progression in the Alzheimer’s Disease Neuroimaging Initiative Alzheimers Dement (Amst). 2018; 10:657-668. . View in PubMed
  • Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial JAMA Neurol. 2018 07 01; 75(7):834-841. . View in PubMed
  • Cerebral amyloid angiopathy in Down syndrome and sporadic and autosomal-dominant Alzheimer’s disease Alzheimers Dement. 2017 Nov; 13(11):1251-1260. . View in PubMed
  • A phase 3 trial of IV immunoglobulin for Alzheimer disease Neurology. 2017 May 02; 88(18):1768-1775. . View in PubMed
  • Outcome Measures for Clinical Trials in Down Syndrome Am J Intellect Dev Disabil. 2017 05; 122(3):247-281. . View in PubMed
  • PET Imaging of Tau Pathology and Relationship to Amyloid, Longitudinal MRI, and Cognitive Change in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI) J Alzheimers Dis. 2017; 60(2):439-450. . View in PubMed
  • A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia J Alzheimers Dis. 2017; 58(2):401-411. . View in PubMed
  • Dissociation of Down syndrome and Alzheimer’s disease effects with imaging Alzheimers Dement (N Y). 2016 Jun; 2(2):69-81. . View in PubMed
  • Improving Memory and Cognition in Individuals with Down Syndrome CNS Drugs. 2016 07; 30(7):567-73. . View in PubMed
  • Targeting tau protein in Alzheimer’s disease Lancet. 2016 12 10; 388(10062):2842-2844. . View in PubMed
  • Advances in Alzheimer’s disease drug development BMC Med. 2015 Mar 25; 13:62. . View in PubMed
  • The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep phenotyping of Alzheimer’s disease biomarkers in down syndrome Front Behav Neurosci. 2015; 9:239. . View in PubMed
  • A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer’s disease Alzheimers Dement. 2014 Sep; 10(5):571-81. . View in PubMed
  • Neuropsychiatric symptoms and regional neocortical atrophy in mild cognitive impairment and Alzheimer’s disease Am J Alzheimers Dis Other Demen. 2014 Mar; 29(2):159-65. . View in PubMed
  • Pro: Are we ready to translate Alzheimer’s disease modifying therapies to people with Down syndrome? Alzheimers Res Ther. 2014; 6(5-8):60.. View in PubMed
  • Preclinical Alzheimer’s disease therapeutics J Alzheimers Dis. 2014; 42 Suppl 4:S545-9. . View in PubMed
  • The National Task Group on Intellectual Disabilities and Dementia Practices consensus recommendations for the evaluation and management of dementia in adults with intellectual disabilities Mayo Clin Proc. 2013 Aug; 88(8):831-40. . View in PubMed
  • Update on Alzheimer’s disease therapeutics Rev Recent Clin Trials. 2013 Jun; 8(2):110-8. . View in PubMed
  • Down’s syndrome and Alzheimer’s disease: towards secondary prevention Nat Rev Drug Discov. 2012 09; 11(9):655-6. . View in PubMed
  • Comparison of the memory performance index with standard neuropsychological measures of cognition Am J Alzheimers Dis Other Demen. 2011 05; 26(3):235-9. . View in PubMed
  • Functional brain imaging in the clinical assessment of consciousness PLoS Biol. 2010 Nov 30; 8(11):e1000548. . View in PubMed
  • The pulse of drug development for Alzheimer’s disease Rev Recent Clin Trials. 2010 Jan; 5(1):57-62. . View in PubMed
  • High-throughput, fully automated volumetry for prediction of MMSE and CDR decline in mild cognitive impairment Alzheimer Dis Assoc Disord. 2009 Apr-Jun; 23(2):139-45. . View in PubMed
  • Recent developments in Alzheimer’s disease therapeutics BMC Med. 2009 Feb 19; 7:7. . View in PubMed
  • Primary care screening for dementia and mild cognitive impairment JAMA. 2008 Mar 12; 299(10):1132; author reply 1133-4. . View in PubMed
  • Biglycan binds to alpha- and gamma-sarcoglycan and regulates their expression during development J Cell Physiol. 2006 Nov; 209(2):439-47. . View in PubMed
  • Case 14: a woman with bilateral Bell’s palsy MedGenMed. 2006 Oct 31; 8(4):23. . View in PubMed
  • Compendium of cerebrovascular diseases Int Rev Psychiatry. 2006 Oct; 18(5):395-407. . View in PubMed
  • Biglycan regulates the expression and sarcolemmal localization of dystrobrevin, syntrophin, and nNOS FASEB J. 2006 Aug; 20(10):1724-6. . View in PubMed
  • Orolingual angioedema associated with ACE inhibitor use after rtPA treatment of acute stroke Neurology. 2005 Dec 27; 65(12):1906. . View in PubMed