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Exploring the Locales of Cognitive Decline

NOMIS Project 2019

— 2023

Despite decades of extensive research, the most prevalent neurodegenerative diseases — Alzheimer’s disease and vascular encephalopathy — remain essentially untreatable, and the fundamental mechanisms of neurodegeneration have yet to be discovered. Based on past experience, progress may come through the deployment of novel technologies — particularly by taking advantage of unbiased, hypothesis-free paradigms.

The project, entitled Exploring the Locales of Cognitive Decline: Cellular and Molecular 3D Atlases of Brain Pathology in Aging and in Neurodegeneration, proposes the combining of high-content three-dimensional morphology with sophisticated fluorochrome chemistry and molecular methods of genome interrogation/perturbation. These techniques will enable the creation of detailed atlases of the cell types that drive damage in various models of neurodegeneration.

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NOMIS Researcher(s)

Professor of neuropathology and director of the Institute of Neuropathology
University of Zurich
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Project News

NOMIS Awardee Adriano Aguzzi and colleague Martin Kampmann have published a review article in Science exploring progress in treatment for neurodegenerative diseases. They ask the question, “What accounts for the […]

NOMIS Awardee Adriano Aguzzi and colleague Elena De Cecco published an article in Science on Oct. 2, 2020, exploring the evolution of prions. Paradigm shifts are drivers of scientific progress, […]

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Project Insights

Abstract: The progressive accumulation of insoluble aggregates of the presynaptic protein alpha-synuclein (α-Syn) is a hallmark of neurodegenerative disorders including Parkinson's disease (PD), Multiple System Atrophy, and Dementia with Lewy Bodies, commonly referred to as synucleinopathies. Despite considerable progress on the structural biology of these aggregates, the molecular mechanisms mediating their
Abstract: Conventional methods of measuring affinity are limited by artificial immobilization, large sample volumes, and homogeneous solutions. This protocol describes microfluidic antibody affinity profiling on complex human samples in solution to obtain a fingerprint reflecting both affinity and active concentration of the target protein. To illustrate the protocol, we analyze the
Abstract: The cellular prion protein PrPC mediates the neurotoxicity of prions and other protein aggregates through poorly understood mechanisms. Antibody-derived ligands against the globular domain of PrPC (GDL) can also initiate neurotoxicity by inducing an intramolecular R208-H140 hydrogen bond (“H-latch”) between the α2-α3 and β2-α2 loops of PrPC. Importantly, GDL that