Biology subjects

Anderson, R. B.

Publications and source records attributed to Anderson, R. B..

3 recordsLinked to original sources

bioRxiv2024

Mapping the impact of age and APOE risk factors for late onset Alzheimer disease on long range brain connections through multiscale bundle analysis

Alzheimers disease currently has no cure and is usually detected too late for interventions to be effective. In this study we have focused on cognitively normal subjects to study the impact of risk factors on their long-range brain connections. To detect vulnerable connections, we devised a multiscale, hierarchical method for spatial clustering of the whole brain tractogram and examined the impact of age and APOE allelic variation on cognitive abilities and bundle properties including texture e.g., mean fractional anisotropy, variability, and geometric properties including streamline length, volume, and shape, as well as asymmetry. We found that the third level subdivision in the bundle hierarchy provided the most sensitive ability to detect age and genotype differences associated with risk factors. Our results indicate that frontal bundles were a major age predictor, while the occipital cortex and cerebellar connections were important risk predictors that were heavily genotype dependent, and showed accelerated decline in fractional anisotropy, shape similarity, and increased asymmetry. Cognitive metrics related to olfactory memory were mapped to bundles, providing possible early markers of neurodegeneration. In addition, physiological metrics such as diastolic blood pressure were associated with changes in white matter tracts. Our novel method for a data driven analysis of sensitive changes in tractography may differentiate populations at risk for AD and isolate specific vulnerable networks.

neuroscience↗

bioRxiv2022

Age-related Macular Degeneration is associated with faster rates of structural brain changes and widespread differences in connectivity

Age-related macular degeneration (AMD) is a prevalent disease impeding vision. More recently, AMD has also been linked to cognitive impairment, such as deficits in language and memory skills. In order to better understand the extent of AMD-related changes in the whole brain structure and connectivity, we have conducted an MRI diffusion acquisition study on 40 participants (20 diagnosed with AMD and 20 controls). These acquisitions were then performed again in a follow up two years later. We developed novel analysis methods for diffusion based tractography and connectomes to better determine which, if any, brain region connections saw the greatest changes between the AMD and the age-matched control groups. Using voxel-based analysis, we identified atrophy in AMD participants in the cuneate gyrus, which has been associated with vision, and the left superior temporal gyrus, which has been associated with language, while later acquisitions compounded this with a deficiency in the bilateral cingulate gyrus, itself linked to higher cognition and memory. These regional atrophy findings support that people with AMD experience widespread neuronal degradation that is not limited to retinal neurons. Regions that saw drastically lowered fractional anisotropy among AMD vs. control included the visual cortex, such as the bilateral occipital lobe and the frontoparietal cortex. Tensor Network Principal Component Analysis (TN-PCA) isolated lingual and temporal connections as important differentiators of AMD connectomes compared to controls, thus supporting our morphometric and texture findings in regions related to vision, but also connectopathies of language and memory brain regions. Bundle based analyses in baseline data revealed that the lingual gyrus had greater spread of tracts overall in the AMD participants, which may be explained by prior reorganization in this area, demonstrating a connection between retinal health and lingual structure. Moreover, we noted group differences in the interhemispheric temporal connections, and lingual cerebellar connections, supporting extensive downstream effects of vision loss. Our bundle-based analyses expand the toolset available for neuroimaging-based phenotyping, and reveal widespread changes in AMD participants beyond brain regions and tractography networks directly involved in vision processing, including those involved in language and memory.

neuroscience↗

bioRxiv2020

The structural dynamics of macropinosome formation and PI3-kinase-mediated sealing revealed by lattice lightsheet microscopy

Macropinosomes are formed by shaping actin-rich plasma membrane ruffles into large intracellular organelles in a phosphatidylinositol 3-kinase (PI3K)-coordinated manner. Here, we utilize lattice lightsheet microscopy and image visualization methods to map the three-dimensional structure and dynamics of macropinosome formation relative to PI3K activity. We show that multiple ruffling morphologies produce macropinosomes and that the majority form through collisions of adjacent PI3K-rich ruffles. By combining multiple volumetric representations of the plasma membrane structure and PI3K products, we show that PI3K activity begins early throughout the entire ruffle volume and continues to increase until peak activity concentrates at the base of the ruffle after the macropinosome closes. Additionally, areas of the plasma membrane rich in ruffling had increased PI3K activity and produced many macropinosomes of various sizes. Pharmacologic inhibition of PI3K activity had little effect on the rate and morphology of membrane ruffling, demonstrating that early production of 3-phosphoinositides within ruffles plays a minor role in regulating their morphology. However, 3-phosphoinositides are critical for the fusogenic activity that seals ruffles into macropinosomes. Taken together, these data indicate that local PI3K activity is amplified in ruffles and serves as a priming mechanism for closure and sealing of ruffles into macropinosomes.

cell biology↗