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
TL;DR: This work considers how brain-network topology shapes neural responses to damage, highlighting key maladaptive processes and the resources and processes that enable adaptation, and shows how knowledge of network topology allows for predictive models of the spread and functional consequences of brain disease.
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The Cellular Phase of Alzheimer’s Disease
TL;DR: Evidence supporting a long, complex cellular phase consisting of feedback and feedforward responses of astrocytes, microglia, and vasculature is reviewed.
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Intramuscular desferrioxamine in patients with Alzheimer's disease
TL;DR: In this paper, a single-blind study was conducted to investigate whether the progression of dementia could be slowed by the trivalent ion chelator, desferrioxamine.
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White matter characterization with diffusional kurtosis imaging.
TL;DR: A physically meaningful interpretation of DKI metrics in white matter regions consisting of more or less parallel aligned fiber bundles is provided by modeling the tissue as two non-exchanging compartments, the intra-axonal space and extra-AXonal space.
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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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Defects in expression of genes related to synaptic vesicle trafficking in frontal cortex of Alzheimer's disease.
Pamela J. Yao,Min Zhu,Eunice I Pyun,Andrew I. Brooks,Stavros Therianos,Victoria E Meyers,Paul D. Coleman +6 more
TL;DR: Microarray analysis of brain tissues from five AD cases revealed a reduced expression of a group of related genes, all of which are involved in synaptic vesicle (SV) trafficking, which suggests a link among SV vesicles-trafficking pathways, synaptic malfunction, and AD pathogenesis.
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The Oral Antidiabetic Pioglitazone Protects from Neurodegeneration and Amyotrophic Lateral Sclerosis-Like Symptoms in Superoxide Dismutase-G93A Transgenic Mice
Burkhard Schütz,Jens Reimann,Lucia Dumitrescu-Ozimek,Karin Kappes-Horn,Gary E. Landreth,Britta Schürmann,Andreas Zimmer,Michael T. Heneka +7 more
TL;DR: Pio-treated transgenic mice revealed improved muscle strength and body weight, exhibited a delayed disease onset, and survived significantly longer than nontreated SOD1-G93A mice, indicating not only morphological but also functional protection of motor neurons by Pio.
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Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta
Gustavo Pigino,Gerardo Morfini,Y. Atagi,Atul Deshpande,C. Yu,Lisa Jungbauer,Mary Jo LaDu,Jorge Busciglio,Scott T. Brady +8 more
TL;DR: Inhibition of FAT by oAβ was prevented by two specific pharmacological inhibitors of CK2, as well as by competition with a CK2 substrate peptide.
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Decrease and structural modifications of phosphatidylethanolamine plasmalogen in the brain with Alzheimer disease.
TL;DR: Both the vinyl ether bond of phosphatidylethanolamine plasmalogen and polyunsaturated fatty acids are major targets in oxidative stress; thus, these specific lipid modifications strongly support the involvement of free radicals in the pathogenesis of AD.
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In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging
George Bartzokis,David L. Sultzer,Jeffrey L. Cummings,Lori E. Holt,Darwood B. Hance,Victor W. Henderson,Jim Mintz +6 more
TL;DR: Basal ganglia ferritin iron levels were significantly increased in the caudate and putamen of patients with AD and a trend toward an increase in the globus pallidus of control subjects, suggesting premorbid iron levels are increased in individuals who develop AD.