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Alzheimer’s Disease Aβ-Amyloid Plaque Morphology Varies According to APOE Isotype

World Journal of Neuroscience 2023年第3期13卷 118-133页

作者： Ina Caesar K. Peter r. Nilsson Per Hammarström Mikael Lindgren Stefan Prokop James Schmeidler Vahram Haroutunian David M. Holtzman patrick r. hof Sam Gandy Department of Neurology Icahn School of Medicine at Mount Sinai New York NY USA Department of Physics Chemistry and Biology Link&#246ping University Link&#246ping Sweden Department of Physics Norwegian University of Science and Technology Trondheim Norway Department of Neuropathology Charité Universit&#228tsmedizin Berlin Berlin Germany Department of Psychiatry Icahn School of Medicine at Mount Sinai New York NY USA Alzheimer’s Disease research Center Icahn School of Medicine at Mount Sinai New York NY USA James J. Peters VA Medical Center Bronx NY USA Nash Family Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai New York NY USA Department of Neurology Hope Center for Neurological Disorders Knight Alzheimer’s Disease Research Center Washington University St. Louis MO USA ronald M. Loeb Center for Alzheimer’s Disease Icahn School of Medicine at Mount Sinai New York NY USA

Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triples the relative risk for AD compared to that of the reference allele, APOE ε3. Methods: We have employed hyperspectral fluorescence imaging with an amyloid-specific, conformation-sensing probe, p-FTAA, to elucidate protein aggregate structure and morphology in fresh frozen prefrontal cortex samples from human postmortem AD brain tissue samples from patients homozygous for either APOE ε3 or APOE ε4. results: As expected APOE ε4/ε4 tissues had a significantly larger load of CAA than APOE ε3/ε3. APOE isoform-dependent morphological differences in amyloid plaques were also observed. Amyloid plaques in APOE ε3/ε3 tissue had small spherical cores and large coronas while amyloid plaques in APOE ε4/ε4 tissues had large irregular and multi-lobulated plaques with relatively smaller coronas. Despite the different morphologies of their cores, the p-FTAA stained APOE ε3/ε3 amyloid plaque cores had spectral properties identical to those of APOE ε4/ε4 plaque cores. Conclusions: These data support the hypothesis that one mechanism by which the APOE ε4 allele affects AD is by modulating the macrostructure of pathological protein deposits in the brain. APOE ε4 is associated with a higher density of amyloid plaques (as compared to APOE ε3). We speculate that multilobulated APOE ε4-associated plaques arise from multiple initiation foci that coalesce as the plaques grow.

关键词： Alzheimer’s Disease Amyloid Apolipoprotein Luminescent Conjugated Oligothiophenes Hyperspectral Separation

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Interactions of primary neuroepithelial progenitor and brain endothelial cells: distinct effect on neural progenitor maintenance and differentiation by soluble factors and direct contact

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Cell research 2007年第7期17卷 619-626页

作者： Miguel A Gama Sosa rita De Gasperi Anne B rocher Gissel M Perez Keila Simons Daniel E Cruz patrick r hof Gregory A Elder Departments of Psychiatry research and Development Service James J. Peters Department of Veterans Affairs Medical Center 130 West Kingsbridge road Bronx New York 10468 USA Departments of Psychiatry research and Development Service James J. Peters Department of Veterans Affairs Medical Center 130 West Kingsbridge road Bronx New York 10468 USA Neuroscience Mount Sinai School of Medicine of New York University New York NY Department of research and Development Service James J. Peters Department of Veterans Affairs Medical Center 130 West Kingsbridge road Bronx New York 10468 USA

Neurovascular interactions are crucial for the normal development of the central nervous system. To study suchinteractions in primary cultures, we developed a procedure to simultaneously isolate neural progenitor and endothelialcell fractions from embryonic mouse brains. Depending on the culture conditions endothelial cells were found to favormaintenance of the neuroprogenitor phenotype through the production of soluble factors, or to promote neuronal differ-entiation of neural progenitors through direct contact. These apparently opposing effects could reflect differential cellularinteractions needed for the proper development of the brain.

关键词： differentiation culture endothelial cells neuroepithelial cells

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