Amyloid PET in Sporadic Early- Versus Late-Onset Alzheimer's Disease: Comparison of the LEADS and ADNI Cohorts
Julien Lagarde MD, PhD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorPiyush Maiti MS
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorDaniel R. Schonhaut PhD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorGanna Blazhenets PhD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorJiaxiuxiu Zhang MS
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorAni Eloyan PhD
Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI
Search for more papers by this authorMaryanne Thangarajah MS
Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI
Search for more papers by this authorAlexander Taurone MS
Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI
Search for more papers by this authorIsabel Elaine Allen PhD
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorDavid N. Soleimani-Meigooni MD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorEhud Zeltzer MD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorCharles Windon MD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorMaison Abu Raya MD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Global Brain Health Institute, The university of California, San Francisco, California, CA
Search for more papers by this authorAgathe Vrillon MD, PhD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorKaren Smith BS
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorRanjani Shankar BS
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorAlinda Amuiri BS
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorSalma Rocha BA
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorDustin B. Hammers PhD
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorJeffrey L. Dage PhD
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorKelly N. Nudelman PhD
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorKala Kirby BS
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorPaul Aisen MD
Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA
Search for more papers by this authorRobert Koeppe PhD
Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, MI
Search for more papers by this authorSusan M. Landau PhD
Department of Neuroscience, University of California, Berkeley, Berkeley, CA
Search for more papers by this authorMaria C. Carrillo PhD
Medical & Scientific Relations Division, Alzheimer's Association, Chicago, IL
Search for more papers by this authorAlexandra Touroutoglou PhD
Frontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Search for more papers by this authorMichael Brickhouse BS
Frontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Search for more papers by this authorPrashanthi Vemuri PhD
Department of Radiology, Mayo Clinic, Rochester, MN
Search for more papers by this authorLaurel Beckett PhD
Department of Public Health Sciences, University of California, Davis, Davis, CA
Search for more papers by this authorRema Raman PhD
Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA
Search for more papers by this authorAlireza Atri MD, PhD
Banner Sun Health Research Institute, Sun City, AZ
Search for more papers by this authorGregory S. Day MD
Department of Neurology, Mayo Clinic, Jacksonville, FL
Search for more papers by this authorRanjan Duara MD
Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, FL
Search for more papers by this authorNeill R. Graff-Radford MD
Department of Neurology, Mayo Clinic, Jacksonville, FL
Search for more papers by this authorLawrence S. Honig MD, PhD
Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, NY
Search for more papers by this authorDavid T. Jones MD
Department of Neurology, Mayo Clinic, Rochester, MN
Search for more papers by this authorJoseph C. Masdeu MD, PhD
Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, TX
Search for more papers by this authorMario F. Mendez MD, PhD
Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA
Search for more papers by this authorKyle Womack MD
Department of Neurology, Washington University in St. Louis, St. Louis, MO
Search for more papers by this authorErik Musiek MD, PhD
Department of Neurology, Washington University in St. Louis, St. Louis, MO
Search for more papers by this authorChiadi U. Onyike MD
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorMeghan Riddle MD
Department of Neurology, Alpert Medical School, Brown University, Providence, RI
Search for more papers by this authorIan M. Grant MD
Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL
Search for more papers by this authorEmily Rogalski PhD
Healthy Aging & Alzheimer's Research Care Center, Department of Neurology, University of Chicago, Chicago, IL
Search for more papers by this authorErik C. B. Johnson MD, PhD
Department of Neurology, Emory University School of Medicine, Atlanta, GA
Search for more papers by this authorStephen Salloway MD
Department of Neurology, Alpert Medical School, Brown University, Providence, RI
Search for more papers by this authorSharon Sha MD
Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA
Search for more papers by this authorR. Scott Turner MD, PhD
Department of Neurology, Georgetown University, Washington, DC
Search for more papers by this authorThomas S. Wingo MD
Department of Neurology, Emory University School of Medicine, Atlanta, GA
Department of Neurology, UC Davis Alzheimer's Disease Research Center, University of California, Davis, Davis, CA
Search for more papers by this authorDavid A. Wolk MD
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorBradford C. Dickerson MD
Frontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Search for more papers by this authorLiana G. Apostolova MD
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, IN
Search for more papers by this authorRenaud La Joie PhD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorCorresponding Author
Gil D. Rabinovici MD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA
Address correspondence to Dr Gil D. Rabinovici, University of California, San Francisco (UCSF), Memory and Aging Center, Box 1207, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94143. E-mail: [email protected]
Search for more papers by this authorthe LEADS Consortium for the Alzheimer's Disease Neuroimaging Initiative
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Search for more papers by this authorJulien Lagarde MD, PhD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorPiyush Maiti MS
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorDaniel R. Schonhaut PhD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorGanna Blazhenets PhD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorJiaxiuxiu Zhang MS
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorAni Eloyan PhD
Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI
Search for more papers by this authorMaryanne Thangarajah MS
Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI
Search for more papers by this authorAlexander Taurone MS
Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI
Search for more papers by this authorIsabel Elaine Allen PhD
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorDavid N. Soleimani-Meigooni MD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorEhud Zeltzer MD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorCharles Windon MD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorMaison Abu Raya MD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Global Brain Health Institute, The university of California, San Francisco, California, CA
Search for more papers by this authorAgathe Vrillon MD, PhD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorKaren Smith BS
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorRanjani Shankar BS
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorAlinda Amuiri BS
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorSalma Rocha BA
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorDustin B. Hammers PhD
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorJeffrey L. Dage PhD
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorKelly N. Nudelman PhD
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorKala Kirby BS
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN
Search for more papers by this authorPaul Aisen MD
Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA
Search for more papers by this authorRobert Koeppe PhD
Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, MI
Search for more papers by this authorSusan M. Landau PhD
Department of Neuroscience, University of California, Berkeley, Berkeley, CA
Search for more papers by this authorMaria C. Carrillo PhD
Medical & Scientific Relations Division, Alzheimer's Association, Chicago, IL
Search for more papers by this authorAlexandra Touroutoglou PhD
Frontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Search for more papers by this authorMichael Brickhouse BS
Frontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Search for more papers by this authorPrashanthi Vemuri PhD
Department of Radiology, Mayo Clinic, Rochester, MN
Search for more papers by this authorLaurel Beckett PhD
Department of Public Health Sciences, University of California, Davis, Davis, CA
Search for more papers by this authorRema Raman PhD
Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA
Search for more papers by this authorAlireza Atri MD, PhD
Banner Sun Health Research Institute, Sun City, AZ
Search for more papers by this authorGregory S. Day MD
Department of Neurology, Mayo Clinic, Jacksonville, FL
Search for more papers by this authorRanjan Duara MD
Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, FL
Search for more papers by this authorNeill R. Graff-Radford MD
Department of Neurology, Mayo Clinic, Jacksonville, FL
Search for more papers by this authorLawrence S. Honig MD, PhD
Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, NY
Search for more papers by this authorDavid T. Jones MD
Department of Neurology, Mayo Clinic, Rochester, MN
Search for more papers by this authorJoseph C. Masdeu MD, PhD
Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, TX
Search for more papers by this authorMario F. Mendez MD, PhD
Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA
Search for more papers by this authorKyle Womack MD
Department of Neurology, Washington University in St. Louis, St. Louis, MO
Search for more papers by this authorErik Musiek MD, PhD
Department of Neurology, Washington University in St. Louis, St. Louis, MO
Search for more papers by this authorChiadi U. Onyike MD
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorMeghan Riddle MD
Department of Neurology, Alpert Medical School, Brown University, Providence, RI
Search for more papers by this authorIan M. Grant MD
Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL
Search for more papers by this authorEmily Rogalski PhD
Healthy Aging & Alzheimer's Research Care Center, Department of Neurology, University of Chicago, Chicago, IL
Search for more papers by this authorErik C. B. Johnson MD, PhD
Department of Neurology, Emory University School of Medicine, Atlanta, GA
Search for more papers by this authorStephen Salloway MD
Department of Neurology, Alpert Medical School, Brown University, Providence, RI
Search for more papers by this authorSharon Sha MD
Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA
Search for more papers by this authorR. Scott Turner MD, PhD
Department of Neurology, Georgetown University, Washington, DC
Search for more papers by this authorThomas S. Wingo MD
Department of Neurology, Emory University School of Medicine, Atlanta, GA
Department of Neurology, UC Davis Alzheimer's Disease Research Center, University of California, Davis, Davis, CA
Search for more papers by this authorDavid A. Wolk MD
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorBradford C. Dickerson MD
Frontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
Search for more papers by this authorLiana G. Apostolova MD
Department of Neurology, Indiana University School of Medicine, Indianapolis, IN
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, IN
Search for more papers by this authorRenaud La Joie PhD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Search for more papers by this authorCorresponding Author
Gil D. Rabinovici MD
Department of Neurology, University of California, San Francisco, San Francisco, CA
Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA
Address correspondence to Dr Gil D. Rabinovici, University of California, San Francisco (UCSF), Memory and Aging Center, Box 1207, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94143. E-mail: [email protected]
Search for more papers by this authorthe LEADS Consortium for the Alzheimer's Disease Neuroimaging Initiative
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
Search for more papers by this authorAbstract
Objective
Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large-scale comparative studies.
Methods
Three hundred ninety-nine cognitively impaired participants younger than 65 years of age from the multicenter Longitudinal Early-onset Alzheimer's Disease Study (LEADS) and 450 cognitively impaired participants older than 65 years from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent clinical assessment, brain magnetic resonance imaging (MRI), and amyloid PET and were included in this study. We compared amyloid PET outcomes (positivity rate based on visual read and quantified tracer uptake expressed as Centiloids [CLs]) between the 2 cohorts and studied their association with age, sex, APOE genotype, and cognition.
Results
The amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI] = 74–82) than in ADNI (71%, 95% CI = 67–75, p = 0.02). Lower Mini-Mental State Examination (MMSE) and APOE4 genotype increased the odds of amyloid positivity in both cohorts. Visually positive scans had higher CLs in LEADS (EOAD, mean = 95.3 ± 26.1) than in ADNI (LOAD, mean = 80.9 ± 36.8, p < 0.0001), predominantly in parietal cortex/precuneus, superior temporal, and frontal cortices. In amyloid-positive patients, (1) CLs were higher in female patients in both cohorts; (2) APOE4 carriership was associated with lower CLs in EOAD, which was not observed in LOAD; and (3) correlations between CLs and MMSE scores were significantly stronger in EOAD than in LOAD.
Interpretation
Differences in the burden of amyloid pathology may contribute to differences in clinical and anatomic patterns in sporadic EOAD and LOAD, and have implications for optimizing therapeutic strategies in each group. ANN NEUROL 2025;98:236–248
Graphical Abstract
Higher amyloid positivity rate and amyloid load in patients with a clinical diagnosis of early-onset Alzheimer's disease (Longitudinal early-onset Alzheimer's disease study [LEADS], n = 399) than late-onset AD (Alzheimer's disease neuroimaging initiative [ADNI], n = 450).
Potential Conflicts of Interest
E.M. is an Assistant Editor for Annals of Neurology. G.D.R. receives research support from Avid Radiopharmaceuticals, GE Healthcare, Genentech, Life Molecular Imaging. The other authors have no competing interests to disclose.
Open Research
Data Availability
The anonymized data that support the findings of this study are available on request from the LEADS data core (https://leads-study.medicine.iu.edu/researchers/leads-data-request-application/) and the ADNI website (https://adni.loni.usc.edu/).
Supporting Information
| Filename | Description |
|---|---|
| ana27233-sup-0001-Supinfo.docxWord 2007 document , 1.4 MB | Data S1. Supporting Information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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