CSF Abeta 3‐42/1‐42 ratio and neurogranin as biomarkers of interest in dementia with Lewy bodies
Jagan A. Pillai, Whitney Popp, Lynn M. Bekris, Ming Wang, Alan J. Lerner, James B Leverenz, Masaru Miyagi- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are the among the most common neuropathologies. Amyloid and tau biomarker changes are often incorporated in the clinical diagnosis of AD. The current DLB criteria does not include robust biofluid biomarkers. However differences in amyloid plaque and CSF neurogranin in DLB has been of interest based on neuropathology and prior CSF reports. Our objective was to determine if Abeta modifications Abeta 3‐42 and Abeta 1‐42 along with neurogranin could be used to differentiate DLB from AD.
Method
This cohort study among 45 MCI stage of AD meeting NIA/AA 2011 criteria and 15 DLB participants meeting the 2017 Mc Keith criteria. We evaluated the CSF levels of Abeta 3‐42, Abeta 1‐42 by Liquid chromatography‐mass spectrometry (LC‐MS/MS) techniques and CSF neurogranin by standard ELISA to explore the differences between groups. Two sample t‐tests both without and with data imputation for samples not meeting lower levels of detection and linear regression models by considering the confounding variables of age, sex and education were assessed.
Result
Mean age 67.67 (SD5.13) years, 33% Female. Mean neurogranin levels in DLB 325.9 (SD 200.34 were lower than in MCI‐AD 707.7 (SD 489.94) pg/ml, (p = 0.0006 from two‐sample t‐test). Mean levels of Abeta 3‐42 were 51.63(SD = 19.6) and 43.63(SD = 13.5)fmol/l, and Abeta 1‐42 848.7 (SD = 248.4) fmol/l and 981.5(SD = 265.0) in DLB and MCI‐AD, respectively and were not significantly different. The ratio of Abeta 3‐42/Abeta 1‐42 was higher in DLB 0.06 (SD = 0.02) than MCI‐AD 0.04 (SD = 0.01) (p = 0.008 from two‐sample t‐test). In the multivariable regression models after adjusting for confounding variables the ratio of Abeta 3‐42/Abeta 1‐42 (Est = 67.19,SE = 29.62, p = 0.02) and neurogranin (Est = ‐0.0069,SE = 0.0026,p = 0.009) were significant discriminators between DLB and MCI‐AD .
Conclusion
Higher ratio of CSF Abeta 3‐42/Abeta 1‐42 and lower CSF levels of neurogranin were noted in the DLB group compared to MCI‐AD. Lower levels of CSF neurogranin in DLB has been reported, while higher ratio of CSF Abeta 3‐42/Abeta 1‐42 in DLB is a novel biomarker finding. Differences in Abeta species in DLB could be potential biomarkers in separating DLB from AD.