Sam Gandy, MD, PhD, the Mount Sinai Professor in Alzheimer’s Disease Research, Professor of Neurology and Psychiatry, and Associate Director of the Alzheimer’s Disease Research Center at Mount Sinai School of Medicine, led the study. Mount Sinai labs led by Patrick R. Hof, MD, Regenstreif Professor of Neuroscience and Vice-Chair for Translational Neuroscience of the Department of Neuroscience and Dara L. Dickstein, PhD, Assistant Professor, Neuroscience also collaborated on the study.
Apolipoprotein E (APOE) is a gene containing instructions needed to make a protein that helps carry cholesterol in the bloodstream. The APOE gene, which comes in several different forms, is related to increased risk of developing Alzheimer’s disease. People with APOE ε4/ε4 gene type have the highest risk of developing the disease and people with APOE ε3/ε3 have a neutral risk. Discovering the important mechanisms underlying how APOE ε4/ε4 increases Alzheimer’s risk has been one of the most vexing mysteries facing Alzheimer’s researchers for over a decade.
Luminescent conjugated oligothiophenes (LCOs) or luminescent conjugated polymers (LCPs), the newly discovered class of biomarkers, can stick to protein structures in the body and emit colors reflecting the different shapes or forms of the proteins. Among other uses, LCPs/LCOs are currently being employed in test tubes, animal models, and autopsied Alzheimer’s brains to study the structure of proteins deposits caused by the disease. The new markers bind to the two well-established hallmarks of Alzheimer’s – beta amyloid plaques and tau tangles – and glow different colors depending on which forms of the deposits they “stick” to (e.g., plaques often “glow” orange, while tangles “glow” yellowish green).
In the study, frozen brain sections from people who died with Alzheimer’s were stained using two LCPs/LCOs: pentamer formyl thiophene acetic acid (pFTAA) and polythiophene acetic acid (PTAA). Using PTAA, the researchers observed that Alzheimer patients with APOE ε4/ε4 gene type had core and cerebrovascular amyloid of different shapes, while in people with APOE ε3/ε3, the two amyloid structures had the same shape. Using pFTAA revealed that tau tangle densities in ε4/ε4 Alzheimer patients that were apparently greater than those with ε3/ε3.
“The findings support our hypothesis that APOE genotype changes amyloid structure,” Dr. Gandy said. “This is important because the different shapes might respond differently to treatments that attempt to clear amyloid deposits from the brain. We already know, for example, that APOE ε4/ε4 patients respond less well to anti-amyloid antibody with bapineuzumab.”
LCOs/LCPs were pioneered by Peter Nilsson, PhD, Assistant Professor of the Department of Chemistry, Linköping University, Sweden. The study also involved collaborating teams from Charité – Universitätsmedizin Berlin, Germany, led by Frank Heppner MD, Director of the Department of Neuropathology and Washington University, St Louis, led by David Holtzman MD, Professor and Chair of Neurology.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2009, U.S. News & World Report ranked The Mount Sinai Hospital among the nation’s top 20 hospitals based on reputation, patient safety, and other patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 530,000 outpatient visits took place.
For more information, visit www.mountsinai.org. Follow us on Twitter @mountsinainyc.About AAICAD
Mount Sinai Press Office | Newswise Science News
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology