Alzheimer's disease as homeostatic responses to age-related myelin breakdown
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TLDR
This work delineates empirically testable mechanisms of action for genes underlying FAD and LOAD and provides "upstream" treatment targets and reframes key observations such as axonal transport disruptions, formation of axonal swellings/sphenoids and neuritic plaques, and proteinaceous deposits as by-products of homeostatic myelin repair processes.Citations
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The connectomics of brain disorders
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White matter characterization with diffusional kurtosis imaging.
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Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease.
Wei Ting Chen,Wei Ting Chen,Ashley Lu,Ashley Lu,Katleen Craessaerts,Katleen Craessaerts,Benjamin Pavie,Carlo Sala Frigerio,Carlo Sala Frigerio,Carlo Sala Frigerio,Nikky Corthout,Xiaoyan Qian,Jana Lalakova,Malte Kühnemund,Iryna Voytyuk,Iryna Voytyuk,Leen Wolfs,Leen Wolfs,Renzo Mancuso,Renzo Mancuso,Evgenia Salta,Evgenia Salta,Sriram Balusu,Sriram Balusu,An Snellinx,An Snellinx,Sebastian Munck,Aleksandra Jurek,José Fernández Navarro,Takaomi C. Saido,Inge Huitinga,Inge Huitinga,Joakim Lundeberg,Mark Fiers,Mark Fiers,Mark Fiers,Bart De Strooper,Bart De Strooper,Bart De Strooper +38 more
TL;DR: Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.
References
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Abnormal brain iron homeostasis in human and animal prion disorders.
Ajay Pal Singh,Alfred Orina Isaac,Xiu Luo,Maradumane L Mohan,Mark L. Cohen,Fusong Chen,Qingzhong Kong,Jason C. Bartz,Neena Singh +8 more
TL;DR: It is demonstrated that prion disease–affected human, hamster, and mouse brains show increased total and redox-active Fe (II) iron, and a paradoxical increase in major iron uptake proteins transferrin (Tf) and transferrin receptor (TFR) at the end stage of disease.
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X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer's disease.
TL;DR: Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12 degrees C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer.
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Expression profiling in APP23 mouse brain: inhibition of Aβ amyloidosis and inflammation in response to LXR agonist treatment
Iliya Lefterov,Angie L. Bookout,Zhu Wang,Matthias Staufenbiel,David J. Mangelsdorf,Radosveta Koldamova +5 more
TL;DR: The results show that LXR agonists could alleviate AD pathology by acting on amyloid deposition and brain inflammation and an upregulation of genes related to lipid metabolism/transport, metabolism of xenobiotics and detoxification is demonstrated.
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FAD mutants unable to increase neurotoxic Abeta 42 suggest that mutation effects on neurodegeneration may be independent of effects on Abeta.
Junichi Shioi,Anastasios Georgakopoulos,Pankaj Mehta,Zen Kouchi,Claudia Litterst,Lia Baki,Nikolaos K. Robakis +6 more
TL;DR: The data suggest that the mechanism by which FAD mutations promote neurodegeneration and AD may be independent of their effects on Aβ production, and several presenilin 1 FAD mutants failed to increase production of A β 42 or the Aβ 42/40 ratio.
Author's response to commentaries Quadratic trajectories of brain myelin content: unifying construct for neuropsychiatric disorders
TL;DR: Bartzokis et al. as discussed by the authors proposed a developmental model of age-related cognitive decline and Alzheimer's disease, which is applicable to a wider range of neurodegenerative and neuropsychiatric disorders.