Amyloid and tau‐PET in early‐onset AD: Baseline data from the Longitudinal Early‐onset Alzheimer's Disease Study (LEADS)

Author:

Cho Hanna123,Mundada Nidhi S.1,Apostolova Liana G.456,Carrillo Maria C.7,Shankar Ranjani1,Amuiri Alinda N.1,Zeltzer Ehud1,Windon Charles C.1,Soleimani‐Meigooni David N.1,Tanner Jeremy A.1,Heath Courtney Lawhn8,Lesman‐Segev Orit H.19,Aisen Paul10,Eloyan Ani11,Lee Hye Sun12,Hammers Dustin B.4,Kirby Kala4,Dage Jeffrey L.4,Fagan Anne13,Foroud Tatiana6,Grinberg Lea T.114,Jack Clifford R.15,Kramer Joel1,Kukull Walter A.16,Murray Melissa E.17,Nudelman Kelly6,Toga Arthur18,Vemuri Prashanthi15,Atri Alireza19,Day Gregory S.20,Duara Ranjan21,Graff‐Radford Neill R.20,Honig Lawrence S.22,Jones David T.1523,Masdeu Joseph24,Mendez Mario25,Musiek Erik13,Onyike Chiadi U.26,Riddle Meghan27,Rogalski Emily J.28,Salloway Stephen27,Sha Sharon29,Turner Raymond Scott30,Wingo Thomas S.31,Wolk David A.32,Koeppe Robert33,Iaccarino Leonardo1,Dickerson Bradford C.34,La Joie Renaud1,Rabinovici Gil D.18,

Affiliation:

1. Memory and Aging Center UCSF Weill Institute for Neurosciences Department of Neurology University of California San Francisco California USA

2. Department of Neurology Gangnam Severance Hospital Yonsei University College of Medicine Seoul Republic of Korea

3. Global Brain Health Institute University of California San Francisco California USA

4. Department of Neurology Indiana University School of Medicine Indianapolis Indiana USA

5. Department of Radiology and Imaging Sciences Center for Neuroimaging Indiana University School of Medicine Indianapolis Indianapolis Indiana USA

6. Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA

7. Medical & Scientific Relations Division Alzheimer's Association Chicago Illinois USA

8. Department of Radiology and Biomedical Imaging University of California San Francisco California USA

9. Department of Diagnostic Imaging Sheba Medical Center Tel HaShomer Israel

10. Alzheimer's Therapeutic Research Institute University of Southern California San Diego California USA

11. Department of Biostatistics Center for Statistical Sciences Brown University Rhode Island USA

12. Biostatistics Collaboration Unit Yonsei University College of Medicine Seoul Republic of Korea

13. Department of Neurology Washington University in St. Louis St. Louis Missouri USA

14. Department of Pathology University of California – San Francisco San Francisco California USA

15. Department of Radiology Mayo Clinic Rochester Minnesota USA

16. Department of Epidemiology University of Washington Seattle Washington USA

17. Department of Neuroscience Mayo Clinic Jacksonville Florida USA

18. Laboratory of Neuro Imaging USC Stevens Neuroimaging and Informatics Institute Keck School of Medicine of USC Los Angeles California USA

19. Banner Sun Health Research Institute Sun City Arizona USA

20. Department of Neurology Mayo Clinic Jacksonville Florida USA

21. Wien Center for Alzheimer's Disease and Memory Disorders Mount Sinai Medical Center Miami Florida USA

22. Taub Institute and Department of Neurology Columbia University Irving Medical Center New York New York USA

23. Department of Neurology Mayo Clinic Rochester Minnesota USA

24. Nantz National Alzheimer Center Houston Methodist and Weill Cornell Medicine Houston Texas USA

25. Department of Neurology David Geffen School of Medicine at UCLA Los Angeles California USA

26. Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore Maryland USA

27. Department of Neurology Alpert Medical School Brown University Rhode Island USA

28. Department of Psychiatry and Behavioral Sciences Mesulam Center for Cognitive Neurology and Alzheimer's Disease Feinberg School of Medicine Northwestern University Chicago Illinois USA

29. Department of Neurology & Neurological Sciences Stanford University Palo Alto California USA

30. Department of Neurology Georgetown University Washington USA

31. Department of Neurology and Human Genetics Emory University School of Medicine Atlanta Georgia USA

32. Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

33. Division of Nuclear Medicine Department of Radiology University of Michigan Ann Arbor Michigan USA

34. Department of Neurology Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA

Abstract

AbstractINTRODUCTIONWe aimed to describe baseline amyloid‐beta (Aβ) and tau‐positron emission tomograrphy (PET) from Longitudinal Early‐onset Alzheimer's Disease Study (LEADS), a prospective multi‐site observational study of sporadic early‐onset Alzheimer's disease (EOAD).METHODSWe analyzed baseline [18F]Florbetaben (Aβ) and [18F]Flortaucipir (tau)‐PET from cognitively impaired participants with a clinical diagnosis of mild cognitive impairment (MCI) or AD dementia aged < 65 years. Florbetaben scans were used to distinguish cognitively impaired participants with EOAD (Aβ+) from EOnonAD (Aβ−) based on the combination of visual read by expert reader and image quantification.RESULTS243/321 (75.7%) of participants were assigned to the EOAD group based on amyloid‐PET; 231 (95.1%) of them were tau‐PET positive (A+T+). Tau‐PET signal was elevated across cortical regions with a parietal‐predominant pattern, and higher burden was observed in younger and female EOAD participants.DISCUSSIONLEADS data emphasizes the importance of biomarkers to enhance diagnostic accuracy in EOAD. The advanced tau‐PET binding at baseline might have implications for therapeutic strategies in patients with EOAD.HIGHLIGHTS 72% of patients with clinical EOAD were positive on both amyloid‐ and tau‐PET. Amyloid‐positive patients with EOAD had high tau‐PET signal across cortical regions. In EOAD, tau‐PET mediated the relationship between amyloid‐PET and MMSE. Among EOAD patients, younger onset and female sex were associated with higher tau‐PET.

Funder

Alzheimer's Association

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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