New infrared sensor extracts amlyloid-beta from blood for early detection of Alzheimer’s.

A major problem of Alzheimer’s disease diagnosis is by the time the first clinical symptoms appear, massive irreversible damage to the brain has already occurred. At that point, symptomatic treatment is the only available option. To have a drug that can significantly inhibit the progress of the disease, blood tests are needed to detect Alzheimer’s in its pre-dementia stages. By applying such drugs at an early stage, dementia could be prevented, or at the very least delayed.  Now, researchers led by Ruhr-Universität Bochum (RUB) have developed an infrared sensor coated with highly specific antibodies which can extract biomarkers for Alzheimer’s from the blood or cerebrospinal fluid. The team state that the infrared sensor analyses of the biomarkers show already pathological changes, which can take place more than 15-years before any clinical symptoms appear. The opensource study is published in the Journal of Biophotonics.

Previous studies show that precise diagnostics are not possible for Alzheimer’s disease until the distribution of all secondary structures is evaluated.  It is known that the structure Amyloid-beta changes in Alzheimer’s patients. In the misfolded, pathological structure, Amyloid beta peptides accumulate, gradually forming visible plaque deposits in the brain that are typical for Alzheimer’s disease. This has been shown to happen more than 15-years before first clinical symptoms appear. Tests that analyse Amyloid-beta peptide are available, such as the enzyme-linked immunosorbent assays (ELISA), however, they can’t provide information on the diagnostically relevant distribution of all secondary structures.  Pathological beta Amyloid plaques can also be temporarily detected by Amyloid PET, but this procedure is comparatively expensive and is accompanied by radiation exposure.  The current study shows that the novel infrared sensor extracts the Amyloid beta peptide from bodily fluids and uses the secondary structure of Amyloid beta as a biomarker.

The current study analysed samples from 141 Alzheimer’s patients. Results show a diagnostic sensitivity of 84% in the blood and 90% in cerebrospinal fluid, compared with the clinical gold standard. Data findings show that the novel test revealed an increase of misfolded biomarkers as spectral shift of Amyloid beta band below threshold, thus diagnosing Alzheimer’s.

The lab also tested the potential for early detection of Morbus Alzheimer’s on a small cohort of patients. The results suggest that even in pre-dementia stages, an increased concentration of misfolded Amyloid beta peptides can be detected in body fluids. The group conclude that Morbus Alzheimer’s may in future be diagnosable in preclinical stages.

The team surmise that their data opens the door for label-free Alzheimer diagnostics in cerebrospinal fluid or blood and add that it can be extended to other neurodegenerative diseases.  For the future, the researchers state that sample analyses for the early detection of Alzheimer’s disease in 800 study participants are being conducted, in order to optimise statistical significance.

Source: Ruhr-Universität Bochum (RUB)

 

An immunologic ATR-FTIR sensor for Abeta peptide secondary structure analysis in complex fluids is presented. The secondary structure change of the Abeta peptide to beta-sheet was proposed as an early event in Alzheimer's disease. The transition may be used for diagnostics of this disease in an early state. We present an Attenuated Total Reflection (ATR) sensor modified with a specific antibody to extract minute amounts of Abeta peptide out of a complex fluid. Thereby, the Abeta peptide secondary structure was determined in its physiological aqueous environment by FTIR-difference-spectroscopy. The presented results open the door for label-free Alzheimer diagnostics in cerebrospinal fluid or blood. It can be extended to further neurodegenerative diseases. An infrared sensor analysing label-free the secondary structure of the Abeta peptide in presence of complex fluids. Gerwert et al 2016.
An immunologic ATR-FTIR sensor for Abeta peptide secondary structure analysis in complex fluids is presented. The secondary structure change of the Abeta peptide to beta-sheet was proposed as an early event in Alzheimer’s disease. The transition may be used for diagnostics of this disease in an early state. We present an Attenuated Total Reflection (ATR) sensor modified with a specific antibody to extract minute amounts of Abeta peptide out of a complex fluid. Thereby, the Abeta peptide secondary structure was determined in its physiological aqueous environment by FTIR-difference-spectroscopy. The presented results open the door for label-free Alzheimer diagnostics in cerebrospinal fluid or blood. It can be extended to further neurodegenerative diseases. An infrared sensor analysing label-free the secondary structure of the Abeta peptide in presence of complex fluids. Gerwert et al 2016.

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