Journal Article

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

Formica, Shane, Tsuang, Debby W., Jain, Lavanya, Litvan, Irene, Berman, Sarah B., Honig, Lawrence S., Lopez, Oscar L., Galasko, Douglas R., Leverenz, James B., Taylor, Angela S., Marder, Karen S., Pillai, Jagan A., Lippa, Carol F., Khrestian, Maria, Bekris, Lynn M., Galvin, James E., Bozoki, Andrea C., Zabetian, Cyrus P., Rao, Stephen, Fleisher, Jori E., Sabbagh, Marwan N., Tuason, Elizabeth D., Irwin, David J., Oguh, Odinachi

2024

Overview

INTRODUCTION The 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. METHODS The cohort was subtyped by cerebrospinal fluid (CSF) ATN category. A subcohort had longitudinal data, and a subgroup was neuropathologically evaluated. RESULTS We 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. DISCUSSION This 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: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Aging / Alzheimer Disease - cerebrospinal fluid / Alzheimer Disease - diagnosis / Alzheimer's disease / Amyloid beta-Peptides - cerebrospinal fluid / ATN longitudinal data / ATN research framework / Autopsies / Biobanks / Biological markers / Biomarkers / Biomarkers - cerebrospinal fluid / Cerebrospinal fluid / cerebrospinal fluid biomarkers / Consortia / Dementia / dementia with Lewy bodies / Humans / Lewy Body Disease - cerebrospinal fluid / Lewy Body Disease - diagnosis / Medical diagnosis / Neurodegeneration / Neuropathology / Neuropsychology / Pathology / Patients / Peptide Fragments - cerebrospinal fluid / Positive emotions / pre‐mortem ATN status / tau Proteins - cerebrospinal fluid