Authors:
Eva Birkmann
1
;
Susanne Aileen Funke
2
;
Detlev Riesner
3
and
Dieter Willbold
1
Affiliations:
1
Institut fuer Physikalische Biologie, Heinrich-Heine-Universitaet; INB-2, Forschungszentrum Juelich, Germany
;
2
INB-2, Forschungszentrum Juelich, Germany
;
3
Institut fuer Physikalische Biologie, Heinrich-Heine-Universitaet, Germany
Keyword(s):
Fluorescence correlation spectroscopy, Alzheimer’ disease, Creutzfeldt-Jakob disease, single particle detection.
Related
Ontology
Subjects/Areas/Topics:
Applications and Services
;
Biomedical Engineering
;
Biomedical Signal Processing
;
Computer Vision, Visualization and Computer Graphics
;
Laser and Opto-Electronics Signal Processing Applications
;
Medical Image Detection, Acquisition, Analysis and Processing
Abstract:
Neurodegenerative diseases like Alzheimer’s disease (AD), prion diseases and others are progressive and lethal. High-molecular weight aggregates of the Amyloid-β-peptides (A) or of the misfolded prion protein (PrP) are found in patients afflicted by AD or prion diseases, respectively. Despite of many attempts, neither a therapy for recovery, nor an early diagnosis at preclinical stages are available. Psychological tests and imaging approaches not directly related with a secure disease marker are in use only for late stages of the disease. The Creutzfeldt-Jakob-disease (CJD), a human prion disease, is caused by accumulation of aggregates consisting of an abnormally shaped version of PrP. CJD is diagnosed with certainty only by neuropathology post mortem. In this study a multidisciplinary development of a novel mode of single particle counting of immobilized Aβ and PrP aggregates as the most direct biomarkers for Alzheimer’s disease and Prion diseases, respectively, is introduced. For
ultrasensitive detection of aggregates, the suitable instrumentation as well as data acquisition and data analysis are developed using single molecule detection and advanced laser scanning fluorescence techniques. In the novel assay development effort biochemistry, detection and analysis were improved to detect single aggregates immobilised on a surface. First results show the improvement of single particle detection of PrP-aggregates of TSE-afflicted cattle and hamsters as well as synthetic Aβ-aggregates.
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