Michael S. Rafii, MD, PhD

Michael S. Rafii, MD, PhD, is Medical Director of the Epstein Family Alzheimer’s Therapeutic Research Institute (ATRI) and Professor of Clinical Neurology at the Keck School of Medicine of the University of Southern California.

Dr. Rafii is an internationally recognized Alzheimer’s disease clinical trialist and a leader in the development of treatments for the genetic form of Alzheimer’s disease that occurs in persons with Down syndrome (DSAD).

He is Principal Investigator of the NIH-funded Alzheimer’s Clinical Trials Consortium–Down Syndrome (ACTC-DS), an international clinical trials network dedicated to accelerating the development of Alzheimer’s therapies for people with Down syndrome.

Dr. Rafii led the Down Syndrome Biomarker Initiative (DSBI), the first study to apply modern Alzheimer’s biomarkers and neuroimaging to adults with Down syndrome. This work helped demonstrate that the biological progression of Alzheimer’s disease in Down syndrome closely parallels other genetic and sporadic forms of the disease and contributed to the scientific foundation for subsequent prevention and treatment trials.

His leadership extends across the broader Alzheimer’s clinical trials field. Dr. Rafii is Associate Director of the NIH-funded Alzheimer’s Clinical Trials Consortium (ACTC) and leads its Medical Safety Unit, which oversees the safety and conduct of one of the world’s largest Alzheimer’s disease clinical trial portfolios. He is also Co-Director of the Clinical Core of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Co-Principal Investigator of the Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET), major national programs advancing Alzheimer’s disease research and treatment.

Dr. Rafii earned his MD and PhD degrees from Brown University, conducted neurogenetics research at Harvard Medical School, completed his neurology residency at the Johns Hopkins Hospital, and completed fellowship training in neurodegenerative diseases at the University of California, San Diego.

Dr. Rafii’s work has been featured in The New York Times, The Washington Post, The Wall Street Journal, Chicago Tribune, The Economist, and NPR. He has also served as medical advisor for the Netflix film Remembering Gene Wilder and the Emmy award-winning television programs Grey’s Anatomy and This is Us..

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

• Life?s end Benefits of CannaBidiol and TetrahYdrocannabinol (LiBBY) Open-Label Extension (OLE) Study
  NIH · R01AG095004 · Aug 15, 2025 – Jul 31, 2028 · Role: Co-Principal Investigator
• Precision Medicine for Inflammatory Treatment for Alzheimer's Disease in Down Syndrome
  NIH · R01AG073979 · Sep 30, 2021 – Aug 31, 2026 · Role: Co-Principal Investigator
• Clinical trials to prevent Alzheimer's Disease in Down Syndrome
  NIH · R33AG066543 · Sep 15, 2019 – Aug 31, 2025 · Role: Principal Investigator
• Clinical trials to prevent Alzheimer's Disease in Down Syndrome
  NIH · R61AG066543 · Sep 15, 2019 – Aug 31, 2021 · Role: Principal Investigator
• ACTIVE IMMUNOTHERAPY FOR COGNITIVE DECLINE IN ADULTS WITH DOWN SYNDROME
  NIH · R01AG047922 · Aug 15, 2014 – Jun 30, 2019 · Role: Principal Investigator
• Alzheimer's Disease Cooperative Study
  NIH · U19AG010483 · Jul 1, 1997 – Feb 28, 2021 · Role: Co-Principal Investigator

• Author Correction: Sleep chart of biological ageing clocks in middle and late life. Nature. 2026 Jul 30.. View in PubMed
• Correction: Serum and cerebral folate are normal in Down Syndrome Regression Disorder. Mol Autism. 2026 Jul 30; 17(1).. View in PubMed
• Delayed Recognition and Stroke-Predominant Presentation in Down Syndrome-Associated Moyamoya Syndrome. Stroke. 2026 Jul 24.. View in PubMed
• Relationships between longitudinal retinal amyloid imaging and amyloid PET in the A4 Trial. Alzheimers Dement (Amst). 2026 Jul-Sep; 18(3):e70422.. View in PubMed
• Facial feature removal in magnetic resonance imaging scans of adults with Down syndrome: A de-facing methodological study. Alzheimers Dement. 2026 Jul; 22(7):e71614.. View in PubMed
• Recent Cochrane review has serious flaws: A perspective of clinicians and researchers from around the world. Alzheimers Dement. 2026 Jul; 22(7):e71696.. View in PubMed
• The Convergence of Down Syndrome and Alzheimer’s Disease – Scientific and Ethical Imperatives. N Engl J Med. 2026 Jun 18; 394(23):2286-2289.. View in PubMed
• Electroencephalographic Normalization as a Biomarker of Clinical Recovery in Down Syndrome Regression Disorder. Ann Clin Transl Neurol. 2026 Jun 07.. View in PubMed
• Imaging and plasma biomarkers for pathological accumulation in Down syndrome. Brain. 2026 Jun 03; 149(6):1944-1957.. View in PubMed
• Exploring automated plasma phospho-tau217 assays for the diagnosis of Down syndrome-related Alzheimer’s disease. Commun Med (Lond). 2026 Jun 02.. View in PubMed
• Immunosuppression in down syndrome regression disorder: a prospective observational cohort study. Brain Commun. 2026; 8(3):fcag203.. View in PubMed
• Ethical challenges of capacity assessment in neurodevelopmental and intellectual disabilities. BMC Med Ethics. 2026 May 25; 27(1).. View in PubMed
• Sleep chart of biological ageing clocks in middle and late life. Nature. 2026 May 13.. View in PubMed
• Beyond amyloid positivity: Biological heterogeneity in the real-world use of lecanemab. J Prev Alzheimers Dis. 2026 Jun; 13(6):100584.. View in PubMed
• Late-life body mass index and amyloid interaction on cognitive decline in unimpaired older adults. J Prev Alzheimers Dis. 2026 May; 13(5):100543.. View in PubMed
• Increase in healthcare utilization and Medicare payment with progression of preclinical Alzheimer’s disease. J Prev Alzheimers Dis. 2026 Jun; 13(6):100547.. View in PubMed
• Precision medicine for Alzheimer’s disease in Down syndrome. Alzheimers Dement. 2026 Apr; 22(4):e71398.. View in PubMed
• A Comparative Effectiveness Study of Lorazepam or IVIg Versus no Treatment for Down Syndrome Regression Disorder. Neurol Ther. 2026 Jun; 15(3):1099-1120.. View in PubMed
• Concordance of Biological and Clinical Staging of Alzheimer Disease Pathology in Down Syndrome. JAMA Neurol. 2026 Mar 01; 83(3):294-296.. View in PubMed
• Decoding Alzheimer’s disease through down syndrome: insights from a genetically defined population. Curr Opin Neurol. 2026 Apr 01; 39(2):210-216.. View in PubMed
• Serum and cerebral folate are normal in Down Syndrome Regression Disorder. Mol Autism. 2026 01 28; 17(1):9.. View in PubMed
• Brain volume trajectories in Down syndrome and autosomal dominant Alzheimer’s disease. Alzheimers Dement. 2026 Jan; 22(1):e71103.. View in PubMed
• Relationship of cholinergic basal forebrain atrophy with the time course of Alzheimer’s disease pathology and cognitive decline in adults with Down syndrome: a longitudinal cohort study. Alzheimers Dement. 2026 Jan; 22(1):e71028.. View in PubMed
• “Being brave, being seen, and having your voice heard”: Perspectives of self-advocates and families toward accessible and impactful research of Alzheimer’s disease in down syndrome. Alzheimers Dement. 2025 12; 21(12):e70999.. View in PubMed
• Plasma Phosphorylated Tau 217 to Identify Preclinical Alzheimer Disease. JAMA Neurol. 2025 Nov 01; 82(11):1122-1134.. View in PubMed
• MRI-based multi-organ clocks for healthy aging and disease assessment. Nat Med. 2026 Jan; 32(1):82-92.. View in PubMed
• A comparison of multiple amyloid PET radiotracers for Down syndrome clinical trials. Brain Commun. 2025; 7(6):fcaf406.. View in PubMed
• Independent effects of white matter lesion volume and APOE ɛ4 on ARIA-H in A4 Study. Alzheimers Dement. 2025 10; 21(10):e70751.. View in PubMed
• Cross-Sectional FDG in Down Syndrome and Autosomal Dominant Alzheimer’s Disease. Ann Neurol. 2025 12; 98(6):1237-1248.. View in PubMed
• Down syndrome and Alzheimer’s disease: insights into biomarkers, clinical symptoms, and pathology. Lancet Neurol. 2025 Sep; 24(9):753-762.. View in PubMed
• Sleep chart of biological aging clocks across organs and omics. medRxiv. 2025 Aug 11.. View in PubMed
• Modernizing diagnosis of Alzheimer’s disease: A review of global trends and Asia-specific perspectives. Alzheimers Dement. 2025 08; 21(8):e70536.. View in PubMed
• Targeting tau for Alzheimers disease through OGA inhibition. J Prev Alzheimers Dis. 2025 Sep; 12(8):100309.. View in PubMed
• Amyloid-lowering immunotherapies for Alzheimer disease: current status and future directions. Nat Rev Neurol. 2025 09; 21(9):490-498.. View in PubMed
• Multi-organ MRI digitizes biological aging clocks across proteomics, metabolomics, and genetics. medRxiv. 2025 Jul 11.. View in PubMed
• Genetically determined Alzheimer’s disease research advances: The Down Syndrome & Autosomal Dominant Alzheimer’s Disease 2024 Conference. Alzheimers Dement. 2025 07; 21(7):e70309.. View in PubMed
• Current advances and unmet needs in Alzheimer’s disease trials for individuals with Down syndrome: Navigating new therapeutic frontiers. Alzheimers Dement. 2025 06; 21(6):e70258.. View in PubMed
• The history of Down syndrome-associated Alzheimer’s disease; past, present, and future. Alzheimers Dement. 2025 06; 21(6):e70158.. View in PubMed
• Relationship between use of anti-platelet agents, oral anti-coagulants, and Aβ burden with cerebral microhemorrhages in cognitively asymptomatic adults. Alzheimers Dement. 2025 05; 21(5):e70167.. View in PubMed
• Brain cholinergic terminal density utilizing [18F]-fluoroethoxybenzovesamicol PET in adults with Down’s syndrome: Relationship to amyloid PET and cognitive performance. Alzheimers Dement. 2025 04; 21(4):e70134.. View in PubMed
• Reflecting on progress, envisioning the future for research in Down syndrome. Lancet. 2025 Mar 20.. View in PubMed
• A head-to-head comparison of multiple amyloid PET radiotracers for Down syndrome clinical trials. medRxiv. 2025 Mar 19.. View in PubMed
• Clinical and neuropathological analysis of Down syndrome over 7 decades of life. J Neuropathol Exp Neurol. 2025 Feb 01; 84(2):168-173.. View in PubMed
• Differences in cholinergic terminal density in adults with Down syndrome compared to neurotypical controls measured by [18F]-fluoroethoxybenzovesamicol positron emission tomography imaging. Neurobiol Aging. 2025 04; 148:50-60.. View in PubMed
• Artificial intelligence-enabled safety monitoring in Alzheimer’s disease clinical trials. J Prev Alzheimers Dis. 2025 Jan; 12(1):100002.. View in PubMed
• Diagnostic abnormalities, disease severity and immunotherapy responsiveness in individuals with Down syndrome regression disorder. Sci Rep. 2024 12 28; 14(1):30865.. View in PubMed
• Effects of the therapeutic correction of U1 snRNP complex on Alzheimer’s disease. Sci Rep. 2024 12 03; 14(1):30085.. View in PubMed
• The amyloid clock: mapping Alzheimer’s disease in Down syndrome. Lancet Neurol. 2024 Dec; 23(12):1173-1174.. View in PubMed
• The mediating role of plasma glial fibrillary acidic protein in amyloid and tau pathology in Down’s syndrome. Alzheimers Dement. 2025 01; 21(1):e14359.. View in PubMed
• Age-Related Changes in the Cholinergic System in Adults with Down Syndrome Assessed Using [18F]-Fluoroethoxybenzovesamicol Positron Emission Tomography Imaging. medRxiv. 2024 Nov 01.. View in PubMed
• The Alzheimer’s Disease Neuroimaging Initiative Clinical Core. Alzheimers Dement. 2024 10; 20(10):7361-7368.. View in PubMed
• Revised criteria for the diagnosis and staging of Alzheimer’s disease. Nat Med. 2024 08; 30(8):2121-2124.. View in PubMed
• Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid. Alzheimers Dement. 2024 08; 20(8):5570-5577.. View in PubMed
• Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimers Dement. 2024 08; 20(8):5143-5169.. View in PubMed
• De novo variants in immune regulatory genes in Down syndrome regression disorder. J Neurol. 2024 Aug; 271(8):5567-5576.. 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 05; 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
• Addressing challenges in health care and research for people with Down syndrome. Lancet. 2024 05 11; 403(10439):1830-1833.. View in PubMed
• Neuroimaging abnormalities associated with immunotherapy responsiveness in Down syndrome regression disorder. Ann Clin Transl Neurol. 2024 04; 11(4):1034-1045.. View in PubMed
• Safety and tolerability of intravenous immunoglobulin infusion in Down syndrome regression disorder. Am J Med Genet A. 2024 05; 194(5):e63524.. View in PubMed
• Safety Profile of a Cognitively Unimpaired Older Population with Elevated Cerebral Amyloid in a 4.5-Year Clinical Trial. J Prev Alzheimers Dis. 2024; 11(4):857-868.. View in PubMed
• Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer’s Disease. J Prev Alzheimers Dis. 2024; 11(4):869-873.. View in PubMed
• Estimating Socio-Economic Status for Alzheimer’s Disease Trials. J Prev Alzheimers Dis. 2024; 11(5):1418-1425.. View in PubMed
• Down Syndrome in a New Era for Alzheimer Disease. JAMA. 2023 12 12; 330(22):2157-2158.. View in PubMed
• Plasma Aβ42/Aβ40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer’s disease. Alzheimers Dement. 2024 02; 20(2):1214-1224.. 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
• Alternative Diagnoses in the Work Up of Down Syndrome Regression Disorder. J Autism Dev Disord. 2025 Jun; 55(6):2085-2091.. 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
• Amyloid-Lowering Monoclonal Antibodies for the Treatment of Early Alzheimer’s Disease. CNS Drugs. 2023 08; 37(8):671-677.. View in PubMed
• Trial of Solanezumab in Preclinical Alzheimer’s Disease. N Engl J Med. 2023 09 21; 389(12):1096-1107.. 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
• 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
• 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
• Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder. Res Sq. 2023 Feb 13.. 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
• Editorial: Appropriate Use Recommendations for Lecanemab. J Prev Alzheimers Dis. 2023; 10(3):356.. 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
• 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
• Early-stage Alzheimer disease: getting trial-ready. Nat Rev Neurol. 2022 07; 18(7):389-399.. 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
• Development of treatments for Down syndrome. Lancet Neurol. 2022 01; 21(1):22-23.. 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
• Increased Autoimmunity in Individuals With Down Syndrome and Moyamoya Disease. Front Neurol. 2021; 12:724969.. 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
• 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
• 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
• 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
• The search for Alzheimer disease therapeutics – same targets, better trials? Nat Rev Neurol. 2020 11; 16(11):597-598. Rafii MS , Aisen PS . 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
• Neurologic complications of Down syndrome: a systematic review. J Neurol. 2021 Dec; 268(12):4495-4509.. 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
• 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
• 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
• 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
• Down syndrome. Nat Rev Dis Primers. 2020 02 06; 6(1):9.. View in PubMed
• Diminished Blood Pressure Profiles in Children With Down Syndrome. Hypertension. 2020 03; 75(3):819-825.. 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

• Santoro, Jonathan
• Aisen, Paul
• Rissman, Robert
• Thompson, Paul
• Schneider, Lon
• Ringman, John