Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease
Year: 2023
Type: article
Study design: Observational Study
Abstract: BACKGROUND: C]UCB-J PET and assessed the association between principal components (PC) subject scores with cognitive performance. METHODS: C]UCB-J binding was measured in 45 amyloid + participants with AD and 19 amyloid- cognitively normal participants aged 55-85. A validated neuropsychological battery assessed performance across five cognitive domains. PCA was applied to the pooled sample using distribution volume ratios (DVR) standardized (z-scored) by region from 42 bilateral regions of interest (ROI). RESULTS: Parallel analysis determined three significant PCs explaining 70.2% of the total variance. PC1 was characterized by positive loadings with similar contributions across the majority of ROIs. PC2 was characterized by positive and negative loadings with strongest contributions from subcortical and parietooccipital cortical regions, respectively, while PC3 was characterized by positive and negative loadings with strongest contributions from rostral and caudal cortical regions, respectively. Within the AD group, PC1 subject scores were positively correlated with performance across all cognitive domains (Pearson r = 0.24-0.40, P = 0.06-0.006), PC2 subject scores were inversely correlated with age (Pearson r = -0.45, P = 0.002) and PC3 subject scores were significantly correlated with CDR-sb (Pearson r = 0.46, P = 0.04). No significant correlations were observed between cognitive performance and PC subject scores in CN participants. CONCLUSIONS: This data-driven approach defined specific spatial patterns of synaptic density correlated with unique participant characteristics within the AD group. Our findings reinforce synaptic density as a robust biomarker of disease presence and severity in the early stages of AD.
Source: NeuroImage Clinical
Institutions: Yale University, VA Connecticut Healthcare System
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,400
Funders: Dana Foundation, Yale University, Georgia Clinical and Translational Science Alliance, National Institutes of Health, School of Public Health, University of California Berkeley, National Institute on Aging, National Institute of Mental Health, National Center for Advancing Translational Sciences
Awards: G1044130170, G196633601, G2434699210, G2515091901, G4245087604, G4541645969, G5351607658, PET Imaging of Synaptic Density in Alzheimers Disease, G6107751520, A Pilot Synaptic Vesicle Glycoprotein 2A (SV2A) PET Study to Evaluate the Effect of CT1812 Treatment on Synaptic Density in Subjects with Mild to Moderate Alzheimer's Disease, Investigation of molecular changes in mGluR5 and SV2A to study synaptic alterations in Alzheimer's disease using PET., G6881567127, Yale Alzheimer Disease Research Center, Molecular Networks Underlying Resilience to Alzheimer's Disease Among APOE E4 Carriers, Yale Alzheimer Disease Research Center, Yale Clinical and Translational Science Award, Claude D. Pepper Older Americans Independence Center at Yale
OpenAlex ID: W4381687545