Search

ABSTRACTPrion diseases, Alzheimer's disease, and Parkinson's disease are age-related neurodegenerative diseases that are characterized by the formation of protein aggregates during the progress of the disease. Although it is still not known whether these aggregates are causative for, or symptoms of, the disease. Many studies show that aggregates or even oligomers of the according proteins are neurotoxic and thus may lead to neurodegeneration. To understand disease-associated or causative mechanisms in respect to protein aggregation, an ultrasensitive tool to quantify these disease-related aggregates is required. In this study we introduce a specificity-enhanced version of surface-FIDA as an approach to count even single aggregates in tissue homogenate and body liquids. [ABSTRACT FROM AUTHOR]

ABSTRACTAlzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common cause of dementia. Aging is among the most significant risk factors. Today, AD can be diagnosed with certainty only post mortem, detecting insoluble β-amyloid peptide (Aβ) aggregates in the patient's brain tissue. We have developed an ultrasensitive assay for early and non-invasive diagnosis of AD. This highly specific and sensitive assay uses fluorescence correlation spectroscopy (FCS) and is sensitive enough to detect even single aggregates in body fluids of AD patients. We investigate the correlation of aggregated Aβconcentrations in body fluids with clinical symptoms of AD. [ABSTRACT FROM AUTHOR]

AbstractPrion diseases are fatal neurodegenerative diseases that occur either spontaneously or genetically or are caused by infection. Spontaneously occuring prion diseases are age related. The infectious agents, called prions, are proteinaceous infectious particles, composed mainly of the host-encoded prion protein (PrP) in a misfolded, insoluble, and aggregated isoform. Advanced glycation end products (AGEs) are well known to contribute to protein misfolding, insolubility, and aggregation. Thus, we studied if AGE-modification could influence PrP aggregation. We analyzed PrP preparations immunochemically to determine if they contain AGE-modified PrP. We also studied the influence of AGE modifications on the PrP aggregation process in vitro. [ABSTRACT FROM AUTHOR]

AbstractToday, Alzheimer disease (AD) can be diagnosed with certainty only post mortem. A biomarker method for early diagnosis of AD is urgently needed. Aβ aggregates are directly involved in AD progression and therefore might be useful as biomarker in body fluids. We have developed an ultrasensitive assay system for the detection of Aβ aggregates in body fluids, called surface-fluorescence intensity distribution analysis (FIDA). Surface-FIDA in its first version was based on fluorescence correlation spectroscopy. Here we show that surface-FIDA can also be performed using a laser scanning microscope setup and is then nicely suitable for the characterization of Aβ aggregates. [ABSTRACT FROM AUTHOR]

ABSTRACTPrion diseases like Creutzfeldt-Jakob disease in humans or scrapie in sheep and goats are infectious neurodegenerative diseases. Their infectious agent, called prion, is composed mainly of aggregated and misfolded prion protein and non-proteinaceous components. An example of such a common non-proteinaceous secondary component of natural prions is the polysaccharide scaffold. We studied the influence of such a polysaccharide on the conformational transition of PrP applying an in vitroconversion system. Here we report that glycogen supports and accelerates PrP amorphous aggregation similar to seeded aggregation and leads to co-aggregates. Furthermore, PrP fibril formation was highly accelerated in the presence of glycogen. [ABSTRACT FROM AUTHOR]