HAI Book 2025 - Flipbook - Page 633
Rani, Nisha
151
Longitudinal rate of change in CSF biomarkers is associated with
subsequent Tau PET burden in Braak stages I and II: Findings from the
BIOCARD study
Nisha Rani1, Abhay Moghekar2, Daniel D. Callow1, Kylie H Alm1, Corinne Pettigrew2, Anja
Soldan2, Michael Miller3, Jiangxia Wang4, Marilyn Albert2, Arnold Bakker1,2
1
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, US
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, US
3
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, US
4
Department of Biostatistics, Johns Hopkins School of Public Health, Baltimore, MD, US
2
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (A´) and tau in the brain, years
before the onset of cognitive symptoms. Understanding the association between early cerebrospinal fluid (CSF)
biomarker changes and subsequent tau pathology based on positron emission tomography (PET) can provide
critical insights for early detection and intervention. This study investigates whether longitudinal changes in CSF
AD biomarkers are associated with tau deposition in medial temporal lobe (MTL) regions reflecting Braak stages I
and II. Analyses included 121 BIOCARD study participants who were cognitively unimpaired at baseline (mean age
57 years). Current tau burden was measured by FMK-6240 PET, and prior levels and trajectories of change in CSF
AD biomarkers were measured with p-tau181, total tau (t-tau), and A´42/A´40 (Lumipulse assay), collected
approximately bi-annually over a mean of 12.8 years prior to the tau PET scan. Linear mixed-effect models
examined how baseline levels and rates of change in these CSF markers relate to tau PET burden, covarying for
age, sex, education, APOE4 genotype, and amyloid positivity. Results indicate significant associations between
higher tau PET burden in Braak stages I and II and elevated baseline levels of p-tau181 (β=0.38, p