ATN cerebrospinal fluid biomarkers in dementia with Lewy bodies: Initial results from the United States Dementia with Lewy Bodies Consortium

Author:

Jain Lavanya1,Khrestian Maria1,Formica Shane1,Tuason Elizabeth D.1,Pillai Jagan A.2,Rao Stephen2,Oguh Odinachi3,Lippa Carol F.3,Lopez Oscar L.4,Berman Sarah B.5,Tsuang Debby W.67,Zabetian Cyrus P.78,Irwin David J.9101112,Galasko Douglas R.13,Litvan Irene13,Marder Karen S.14,Honig Lawrence S.13,Fleisher Jori E.15,Galvin James E.16,Bozoki Andrea C.17,Taylor Angela S.18,Sabbagh Marwan N.19,Leverenz James B.2,Bekris Lynn M.1

Affiliation:

1. Genomic Medicine Institute Cleveland Clinic Cleveland Ohio USA

2. Cleveland Clinic Lou Ruvo Center for Brain Health Cleveland Clinic Cleveland Ohio USA

3. Cleveland Clinic Lou Ruvo Center for Brain Health‐Las Vegas Cleveland Clinic Las Vegas Nevada USA

4. Cognitive Disorders & Comprehensive Alzheimer's Disease Center Thomas Jefferson University Philadelphia Pennsylvania USA

5. Department of Neurology University of Pittsburgh Pittsburgh Pennsylvania USA

6. Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine Seattle Washington USA

7. Geriatric Research, Education, and Clinical Center VA Puget Sound Health Care System Seattle Washington USA

8. Department of Neurology University of Washington School of Medicine Seattle Washington USA

9. Department of Neurology University of Pennsylvania Health System Philadelphia Pennsylvania USA

10. Digital Neuropathology Laboratory Philadelphia Pennsylvania USA

11. Lewy Body Disease Research Center of Excellence Philadelphia Pennsylvania USA

12. Frontotemporal Degeneration Center Philadelphia Pennsylvania USA

13. Department of Neurosciences University of California San Diego California USA

14. Columbia University Irving Medical Center New York New York USA

15. Department of Neurological Sciences Rush Medical College Chicago Illinois USA

16. Department of Neurology Comprehensive Center for Brain Health University of Miami Miller School of Medicine Miami Florida USA

17. Department of Neurology University of North Carolina Chapel Hill North Carolina USA

18. Lewy Body Dementia Association Lilburn Georgia USA

19. Department of Neurology Barrow Neurological Institute Phoenix Arizona USA

Abstract

AbstractINTRODUCTIONThe National Institute on Aging – Alzheimer's Association (NIA‐AA) ATN research framework proposes to use biomarkers for amyloid (A), tau (T), and neurodegeneration (N) to stage individuals with AD pathological features and track changes longitudinally. The overall aim was to utilize this framework to characterize pre‐mortem ATN status longitudinally in a clinically diagnosed cohort of dementia with Lewy bodies (DLB) and to correlate it with the post mortem diagnosis.METHODSThe cohort was subtyped by cerebrospinal fluid (CSF) ATN category. A subcohort had longitudinal data, and a subgroup was neuropathologically evaluated.RESULTSWe observed a significant difference in Aβ42/40 after 12 months in the A+T− group. Post mortem neuropathologic analyses indicated that most of the p‐Tau 181 positive (T+) cases also had a high Braak stage.DISCUSSIONThis suggests that DLB patients who are A+ but T− may need to be monitored to determine whether they remain A+ or ever progress to T positivity.Highlights Some A+T‐ DLB subjects transition from A+ to negative after 12‐months. Clinically diagnosed DLB with LBP‐AD (A+T+) maintain their positivity. Clinically diagnosed DLB with LBP‐AD (A+T+) maintain their positivity. Monitoring of the A+T‐ sub‐type of DLB may be necessary.

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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