Biology subjects

Elison, J.

Publications and source records attributed to Elison, J..

5 recordsLinked to original sources

bioRxiv2026

Ontological Analysis of Brain Proteostasis Highlights the Sex-Dependent Trajectory of ApoE Isoform-Specific Regulation

Apolipoprotein E (ApoE) is the strongest genetic predictor of Alzheimers disease (AD) risk, with ApoE4 increasing and ApoE2 decreasing risk relative to ApoE3. Using a global LC-MS proteomic approach, we integrated protein abundance and kinetics in Human-APOE knock-in mice for young (3-month) and aged (18-month) cohorts to quantify the changes in steady-state proteostasis. By mapping 6,052 identified proteins and 3,986 associated turnover rates into ontological groups, we observed that vesicle trafficking and mitochondrial dysregulation occur as early as 3 months in ApoE4 mice accompanied by hyperactive metabolism that eventually reduces with age. In contrast, young and old ApoE2 mice retain similar signatures to ApoE3 mice in metabolic, mitochondrial, cellular regulation, and membrane trafficking ontologies. We found that females had more isoform-induced ontological changes relative to ApoE3, providing insight into sex-dependent vulnerabilities. Our global proteomic approach for ApoE proteostasis crucially unifies independent literature observations while providing turnover kinetics to uncover the underlying mechanism behind abundance changes. Data are available via ProteomeXchange with identifier PXD079261. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/735293v1_ufig2.gif" ALT="Figure 1000"> View larger version (45K): org.highwire.dtl.DTLVardef@28ebfforg.highwire.dtl.DTLVardef@9dc6f2org.highwire.dtl.DTLVardef@704577org.highwire.dtl.DTLVardef@e0b0e2_HPS_FORMAT_FIGEXP M_FIG C_FIG O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/735293v1_ufig1.gif" ALT="Figure 1001"> View larger version (48K): org.highwire.dtl.DTLVardef@17d0474org.highwire.dtl.DTLVardef@af771borg.highwire.dtl.DTLVardef@1b49f67org.highwire.dtl.DTLVardef@14d3aa2_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2026

Variation in infant subcortical brain development from 6 to 12 months in Down syndrome

IntroductionDown syndrome (DS), arising from Trisomy 21, is the most common genetic condition associated with intellectual disability. While smaller total brain volumes have been consistently observed in DS, no longitudinal neuroimaging studies have examined volumetric brain development in DS during infancy, a period of rapid neural growth when interventions may have the greatest impact. MethodHigh-resolution T1- and T2-weighted images were acquired during natural sleep in a multisite longitudinal cohort of 44 infants with DS and 39 control infants without DS at ages 6 and 12 months. Neuroimaging data were harmonized to reduce batch effects, and a novel deep-learning, repeated-measures segmentation approach was applied to optimize neuroanatomical segmentations. Total intracranial volume (ICV) and bilateral absolute subcortical volumes (amygdala, caudate, hippocampus, pallidum, putamen, thalamus) were first directly compared in infants with and without DS at 6 and 12 months. Hierarchical linear modeling (HLM) evaluated longitudinal group differences for each structure, accounting for sex, gestational age, and laterality. Subcortical group differences estimated by HLM were also compared to group differences in total ICV. ResultsICV in infants with DS was lower than controls at 6 months (12.6%; p<.001) and 12 months (16.3%; p<.001). Subcortical structures displayed a range of lower volumes (6.9%-13.1%; ps[≤].003) in infants with DS, although the caudate and putamen were exceptions. Caudate volumes were on average lower in DS but not significantly different from controls, while putamen volumes were on average higher in DS but not significantly different from controls, except for the right putamen, which was significantly larger (5.3%; p=.018) at 6 months. In HLM, ICV and all subcortical structures showed slower growth in DS from 6 to 12 months, except for the amygdala and putamen, which displayed similar growth rates to controls. DS-associated reductions in subcortical volumes were similar in magnitude to ICV, although 12-month caudate and 6- and 12-month putamen volumes were enlarged relative to ICV. ConclusionInfants with DS exhibited substantially reduced ICV and widespread reductions in subcortical volumes and growth from 6-12 months. Across a range of volumetric differences, findings were most distinct in the basal ganglia, for which volume reductions were attenuated in the caudate, while the putamen was uniquely enlarged with comparable growth to controls. These observations support early regional specificity in the neural impact of Trisomy 21 and underscore the utility of infant neuroimaging to inform biologically based interventions and clinical trial readiness in DS.

neuroscience↗

bioRxiv2026

Visual Cortical Response Variability in Infants at High Familial Likelihood for Autism

Visual processing undergoes rapid development in the first year of life, supporting the emergence of higher-order cognitive, language, and motor functions. Visual evoked potentials (VEPs) provide a non-invasive measure of visual system maturation that may shed light on heterogeneous developmental trajectories among infants at high familial likelihood for autism. Infants with an older sibling with autism spectrum disorder (N = 177 at 6 months; N = 132 at 12 months) participated in the Infant Brain Imaging Study-Early Prediction (IBIS-EP) study. Pattern-reversal VEPs were recorded at 6 and 12 months, and developmental skills were assessed at 24 months using the Bayley Scales of Infant and Toddler Development (Bayley-4). VEP components (P1 and N1) were characterized by their amplitude and latency, as well as trial-to-trial variability in these measures. Associations with 24-month cognitive, language, and motor scores were examined using general linear models controlling for age, site, sex, and trial count. Robust VEPs were observed at both time points, with age-appropriate morphology and expected developmental changes, including decreases in P1 latency and amplitude from 6 to 12 months. Greater trial-to-trial variability in P1 latency at both time points was associated with higher cognitive and language scores at 24 months. In contrast, conventional measures of mean P1 latency and amplitude were not associated with developmental outcomes. These findings suggest that temporal variability in early visual responses may index adaptive sensory-circuit flexibility during a period of rapid experience-dependent development. VEP response-timing variability may therefore provide an early mechanistic marker of sensory-circuit organization relevant to later developmental trajectories. Research HighlightsO_LIGreater trial-to-trial variability in visual cortical response timing was associated with higher cognitive and language scores in infants at high familial likelihood for autism. C_LIO_LIConventional average VEP measures were unrelated to outcomes, suggesting temporal variability may more sensitively capture relevant neural-circuit differences in this population. C_LIO_LIGreater variability in early visual responses may reflect adaptive sensory-circuit flexibility during a critical period of neurodevelopment. C_LIO_LIVEP response-timing measures provide an early mechanistic window into sensory-circuit organization and its relation to later developmental trajectories. C_LI

neuroscience↗

bioRxiv2025

BabyPy: a brain-age model for infancy, childhood and adolescence

Withdrawal StatementThe authors have withdrawn this manuscript because during the peer-review process, they realised that their interpretation of the brain-age model presented in this paper was not fully accurate. While the analyses, statistics, and results remain valid, their interpretation of the internal test set performance metrics was inaccurate due to the non-linear shape of the distribution. In other words, although the overall R{superscript 2} is correctly reported as 0.80, this value does not capture the variability of the metrics across different age bins. For this reason, the authors are withdrawing the preprint. Therefore, the authors do not wish this work to be cited as reference for the project. The authors aim to re-run the analysis to provide a more robust version of the model and a new DOI will be linked on this page once the revised work is available. If you have any questions, please contact the corresponding author.

neuroscience↗

bioRxiv2024

Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain

Apolipoprotein E (ApoE) polymorphisms modify the risk of neurodegenerative disease with the ApoE4 isoform increasing and ApoE2 isoform decreasing risk relative to the wild-type control ApoE3 isoform. To elucidate how ApoE isoforms alter the proteome, we measured relative protein abundance and turnover in transgenic mice expressing a human ApoE gene (isoform 2, 3, or 4). This data provides insight into how ApoE isoforms affect the in vivo synthesis and degradation of a wide variety of proteins. We identified 4849 proteins and tested for ApoE isoform-dependent changes in the homeostatic regulation of [~]2700 ontologies. In the brain, we found that ApoE4 and ApoE2 both lead to modified regulation of mitochondrial membrane proteins relative to the wild-type control ApoE3. In ApoE4 mice, this regulation is not cohesive suggesting that aerobic respiration is impacted by proteasomal and autophagic dysregulation. ApoE2 mice exhibited a matching change in mitochondrial matrix proteins and the membrane which suggests coordinated maintenance of the entire organelle. In the liver, we did not observe these changes suggesting that the ApoE-effect on proteostasis is amplified in the brain relative to other tissues. Our findings underscore the utility of combining protein abundance and turnover rates to decipher proteome regulatory mechanisms and their potential role in biology.

biochemistry↗