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Alzheimer's Disease - OSTI GOV

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Last Updated: 14 April 2022

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Deep learning for Alzheimer's disease: Mapping large-scale histological tau protein for neuroimaging biomarker validation

Abnormal tau inclusions are characteristic of Alzheimer's disease and predictors of clinical decline. Several tau PET tracers are available for neurodegenerative disease research, opening up avenues for molecular diagnosis in vivo. PET signal validation is difficult because it requires a large-scale, voxel correlation between PET and histological results, which makes it difficult to determine. To produce quantitative, 3D density maps, we used a computational pipeline to find and segment particles of interest in billion-pixel digital pathology images. Thousands of slides from two complete human brains were successfully processed and immunostained with three phospho-tau antibodies, spanning many terabytes of images. For AT100, AT8, and MC1, respectively, our artificial neural network estimated tau removal from brain photographs, which results in ROC AUC of 0. 87, 0. 85, and 0. 91 for AT100, AT8, and MC1, respectively. As a way to facilitate the testing of PET tracers, we present an end-to-end pipeline that will produce terabytes-wide 3D tau inclusion density maps co-registered to MRI.

Source link: https://www.osti.gov/biblio/1855218


Investigating the clinico-anatomical dissociation in the behavioral variant of Alzheimer disease

Patients with bvAD were compared to other diagnostic groups on glucose metabolism and metabolic connectivity as measured by [18 F]FDG-PET] and subcortical gray matter and white matter hyperintensity volumes determined by MRI. bvAD and tAD displayed the most prominent temporoparietal hypometabolism compared to controls, but not differ in direct comparisons. However, overlaying statistical maps from comparisons of patients and controls revealed greater frontoinsular hypometabolism in bvAD than tAD, partially matching bvFTD. BvAD's anterior default mode network presence was higher than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions, according to the bvAD. A semblance of bvAD to tAD was closer in tvHD to bvFTD than in bvFD, with larger amygdalar volumes in bvAD than in tAD, as shown by an analyses of WMH and subtactical volume in bvAD and tAD, as well as higher amygdalar volumes in bvAD and tAD respectively. FDG posterior-DMN-ratios were the top-three discriminators for bvAD vs. bvFTD. The top-3 for bvAD vs. tAD were amygdalar volume, MRI anterior-DMN-ratios bvAD ratios bvAD, amygdalar volume, and tAD vs. tAD, amygdalar volume, bvAD vs. tAD; amygdalar volume, vs. tAD, amygd.

Source link: https://www.osti.gov/biblio/1816073


Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model

Myeloid cells are the primary or significantly expressed in many risk genes for Alzheimer's disease. Following microglial depletion, plaques fail to form in the parenchymal space following microglial depletion, except in areas with surviving microglia. The absence of microglia has also altered gene expression in the 5xFAD hippocampus. We introduce PLX5622's design, manufacture, and effectiveness, which allows for sustained microglial depletion and discovery of microglia in initiating plaque pathogenesis.

Source link: https://www.osti.gov/biblio/1624183


Modeling Alzheimer’s Disease Progression with Fused Laplacian Sparse Group Lasso

Alzheimer's disease, the most common type of dementia, not only puts a financial strain on the health care system, but also a psychological and emotional burden on patients and their families. We introduce multi-task learning with fused Laplacian sparse group lasso model, which can identify biomarkers closely related to cognitive function due to its scarcity-inducing property, as well as a general weighted dependency graphs among the tasks.

Source link: https://www.osti.gov/biblio/1557047


Amyloid-β induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer’s disease

Although current studies link NLRP1 genetic variants with AD, the role of NLRP1 in AD pathogenesis is still unclear. Moreover, we used non-viral small-interfering RNA in vivo in a cellular Appetitone/caspase-1 brain, and discovered that these NLRP1 or caspase-1 deficiency mice promoted marked cerebral erythritisis and reversed cognitive impairments in a clinical setting. Our results, taken together, indicate an important role for NLRP1/caspase-1 signaling in AD progression, as well as the modulation of NLRP1 inflammasome as a promising treatment for AD therapy.

Source link: https://www.osti.gov/biblio/1623745


Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer's disease peptide β-amyloid (1–42)

For decades, a correlation between elevated levels of iron and Alzheimer's disease pathology has been apparent, including AD lesions made of the peptide b-amyloid peptide b-amyloid peptide. We investigate the relationship between Ab and synthetic iron, reminiscent of ferric iron stores in the brain using X-ray microspectroscopy, X-ray absorption spectroscopy, electron microscopy, and spectrophotometric iron quantification methods. We discovered Ab to be able of accumulating iron within amyloid aggregates, with this process resulting in Ab-mediated iron reduction to a redox-active iron phase. These findings show that Ab can accumulate iron, providing an explanation for previously observed local rises in iron concentrations associated with AD lesions. In addition, the ability of iron to produce redox-active iron phases from ferric precursors could account for both the redox-active iron found in AD tissue and the increased levels of oxidative stress typical of AD.

Source link: https://www.osti.gov/biblio/1625586


Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease

In vivo retention of PiB in brains of Alzheimer's disease patients with Alzheimer's disease has a regional distribution that is similar to Ab deposits' distribution observed post-mortem. The preponderance of 6 -CN-PiB binding in Alzheimer's disease brain tissue sections, including one Alzheimer's disease patient who had undergone PiBET imaging ten months before death, was then compared to region- and substrate-specific binding of the highly fluorescent PiB derivative 6 -PiB in plaques immunoreactive to either Ab42 or Ab40, as well as in vivo PETretention samples. While diffuse plaques in the prefrontal and temporal cortices were less prominently identified, amorphous Ab plaques in the cerebellum were not detectable with 6 -CN-PiB, including those in caudate nucleus and pre-subpoes, were not detected with CN-PiB. There was a strong correlation between [3 H]PiB binding and insoluble Ab peptide levels in Alzheimer's disease brain tissue homogenates. The strong direct correlation of in vivo PiB preservation with region-matched quantitative studies of Ab plaques in the same study supports the integrity of PiB-PET imaging as a tool for in vivo assessment of Ab plaque burden.

Source link: https://www.osti.gov/biblio/1625298

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions