Cellular Circadian Period and its Deviation Associate with Alzheimer’s Disease and Brain Aging. Roh et al.
Description
Research Hypothesis We hypothesized that intrinsic circadian rhythms measured at the cellular level, specifically the fibroblast circadian period and its deviation from 24 h (Δ-period), are associated with Alzheimer’s disease (AD)-related pathology, aging, neurodegeneration, cognitive decline, and clinical progression. What the Data Show In 135 older adults with cognitive concerns, dermal fibroblasts were assayed using BMAL1-luciferase bioluminescence to estimate cellular circadian period and Δ-period. A longer period correlated with higher plasma pTau-217, NfL, GFAP and greater medial temporal lobe atrophy, while a greater Δ-period associated with older age, worse cognition across multiple domains (language, memory, visuospatial), and more widespread gray-matter loss. Longitudinally, both a longer period (HR 4.4) and greater Δ-period (HR 2.7) predicted faster clinical worsening (CDR-SB progression). What the Data Are The dataset is organized into five anonymized participant-level files: 1. Demographics and Covariates (1_demographics_covariates.xlsx) Variables: subject_id, age, sex, education, diabetes, hypertension, depressive_symptoms_SGDS_score, cognitive_enhancer_use, antidepressant_use, benzodiazepine_use, antipsychotics_use, sleep_medication_use, nutrition_MNA_score, physical_activity_IPAQ_score, apoe_e4_carrier, mmse_score, cdr_sum_of_box. 2. Plasma Biomarkers & Imaging Variables (2_neuroimaging_plasma_biomarkers.xlsx) Variables: subject_id, A_Amyloid_PET_Positivity, A_Amyloid_PET_Centiloid, T_Plasma_pTau217, N_Plasma_NfL, N_MRI_Neurodegeneraion, I_Plasma_GFAP, V_MRI_periventricular, V_MRI_deep_white_matter. 3. Cognition (3_cognition.xlsx) Variables: subject_id, general_cognition, language_function, verbal_memory_function, visuospatial_memory_function, frontal_executive_function. 4. Cellular Circadian Metrics (4_cell_circadian_metrics.xlsx) Variables: subject_id, cellular_period, cellular_delta_period. 5. Longitudinal Follow-up (5_longitudinal_data.xlsx) Variables: subject_id, cellular_period, cellular_period_Q1_Q234_Q5, cellular_delta_period, cellular_delta_period_0.75_binary, clinical_progression_yn, clinical_progression_fu_time. Access and Ethics All data are de-identified and IRB-approved (AJOUIRB-SUR-2021-038) with informed consent. Data are provided for research purposes only; please cite the dataset and associated manuscript when reusing.
Files
Steps to reproduce
Continuous variables were reported as the median with interquartile range (IQR) after verifying normality using the Shapiro–Wilk test. Group comparisons were conducted using the student’s t-test for normally distributed variables and the Mann–Whitney U test for non-normally distributed variables, while categorical variables were compared using the chi-squared test. Exploratory correlation analyses were performed to assess associations between cellular circadian period and various biomarkers or cognitive functions, using Pearson’s or Spearman’s correlation coefficients based on data distribution. The Benjamini–Hochberg method was applied to control the false discovery rate (FDR), with significant correlations identified at FDR-corrected p-values < 0.05. Variables showing potential significance underwent further analysis using a generalized linear model (GLMs) to adjust for confounding factors. Associations between cellular circadian period and neurodegeneration were examined using voxel-based morphometry, with anatomical regions defined by the Automated Anatomical Labeling Atlas 3 (AAL3). Survival analysis was conducted using a Cox proportional hazards model to evaluate the relationship between cellular circadian measures and clinical progression, with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated after adjusting for covariates. All statistical analyses were performed using R (version 4.2.0; R Foundation for Statistical Computing, Vienna, Austria) and SPSS (version 25.0; IBM, Armonk, NY, USA).
Institutions
- Ajou University School of Medicine and Graduate School of Medicine