Combined assay for differential diagnosis of alzheimer's disease

A technology for Alzheimer's disease and differential diagnosis, applied in the field of combined immuno-infrared assays, which can solve the problem of no spectral decomposition, inability to reveal direct secondary structure changes of proteins, and inability to provide a robust platform for protein secondary structure transition analysis, etc. question

Inactive Publication Date: 2019-08-23
RUHR UNIV BOCHUM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Since these techniques only provide kinetic information but no spectral decomposition, they cannot reveal direct secondary structure changes within proteins
Other techniques such as surface-enhanced infrared absorption (SEIRA) spectroscopy can theoretically provide spectral resolution, but measurement reproducibility is very challenging due to the preparation of rough gold surfaces, thus failing to provide a robust platform for the analysis of protein secondary structure transitions

Method used

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  • Combined assay for differential diagnosis of alzheimer's disease
  • Combined assay for differential diagnosis of alzheimer's disease
  • Combined assay for differential diagnosis of alzheimer's disease

Examples

Experimental program
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Effect test

Embodiment 1

[0080] Example 1: Aβ and Tau protein secondary structure profiles for precise DC and DAT discrimination.

[0081] The performed study included 300 samples from 61 DC and 39 DAT patients. Details regarding the patient's differential diagnosis were described previously (Nabers et al., Anal. Chem. Doi: 10.1021 / acs.analchem.5b04286 (2016)). Typically, the patient set is divided into DC and DAT subjects. The DAT group was further subdivided into early, moderate, and severe stages of Alzheimer's disease. For a minority of DC patients, a full differential diagnosis is available, including those with dementias due to origins other than Alzheimer's disease, such as Parkinson's disease or vascular dementia. To analyze the secondary structure distribution of Aβ and Tau in CSF and / or plasma, the two biomarkers were extracted from the respective fluids by the immunoinfrared sensor described by Nabers et al. (Nabers et al., Anal. Chem. Doi: 10.1021 / acs.analchem.5b04286(2016)). Thus, ...

Embodiment 2

[0082] Example 2: Combination assay for differential diagnosis of DC and DAT.

[0083] Combined data analysis also offered the potential to subdivide the two diagnostic groups. this is in Figure 5 is schematically shown in . For example, Aβ from CSF and plasma showed an amide I maximum greater than or equal to 1643 cm -1 , but the maximum value of Tauamide I is lower than 1643cm -1 , in this case another type of dementia can be indicated by combined immuno-infrared assays ( Figure 5 ). Conversely, when Aβ amide I maxima from CSF and plasma are below the marker band but Tau maxima are above this, an early state of DAT will be indicated. This procedure was applied to both diagnostic groups in our study. Amide I maxima for Aβ from CSF demonstrated a higher maxima than Tau from CSF in 69% of all DC cases. This effect can be explained by the higher disordered nature of Tau protein compared to Aβ. On the other hand, the maximum value of Aβ was lower in 25% of all DC cases ...

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Abstract

The invention provides a combined immuno-infrared assay for the differential diagnosis and sub classification of Alzheimer's disease into different disease stages. The method can be applied for assured disease diagnostics and patient stratification. The assay considers the label-free detection of the change within the Amyloid-beta peptide and Tauprotein secondary structure distribution in bodily fluids. This secondary structure change from native to -sheet enriched isoforms appears years before clinical disease manifestation. Now, the combined method utilizes this shift for diagnostics basedon liquid biopsies.

Description

[0001] The present invention provides a combined immunoinfrared assay for differential diagnosis and subclassification of Alzheimer's disease into different disease stages. This approach can be used to ensure disease diagnosis and patient stratification. This test allows for label-free detection of changes in the distribution of amyloid-beta peptide and Tau protein secondary structure in body fluids. This secondary structure change from native to β-sheet-enriched isoforms occurs delayed for Aβ and Tau, but many years before clinical disease manifestation. Combinatorial approaches now exploit this displacement for liquid biopsy-based diagnostics. Background technique [0002] Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, affecting more than 35 million people worldwide (Prince et al., London, UK doi:10.1111 / j.0963-7214.2004.00293.x(2015 )). Differential diagnosis and subclassification of AD, especially early or prodromal stages of the disease,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68
CPCG01N21/552G01N33/6896G01N2333/4709G01N2800/2821G01N2800/56
Inventor K.格沃特A.纳伯斯J.沙尔特纳
Owner RUHR UNIV BOCHUM
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