Platelet Protein Biomarker Normalization for Alzheimer Diagnosis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current diagnostic methods for Alzheimer's disease are challenging due to the difficulty in accurately diagnosing early-stage neuronal disorders, as they often rely on invasive sample materials like cerebrospinal fluid, and there is a need for peripheral biomarkers from easily obtainable patient samples to aid in simple and accurate diagnosis.
Innovation Solution
The use of Mitogen-activated protein kinase 1 (ERK2) to normalize biological variation in the expression levels of platelet proteins, specifically monoamine oxidase-B, coagulation factor XIIIa, tropomyosin, WD-repeat protein 1, and apolipoprotein E, in a platelet sample to aid in the diagnosis of Alzheimer's disease through quantification and comparison to control values.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If diagnostic methods use invasive sample materials like cerebrospinal fluid, then diagnostic accuracy can be improved, but patient discomfort and procedural complexity increase
Solution Approach 1:
The patent uses platelets as an intermediary biomarker source. Instead of directly analyzing cerebrospinal fluid (invasive), the method measures protein expression levels in platelets (non-invasive blood draw) that reflect neuronal pathology. Plateacts serve as a mediator between easily obtainable blood samples and the actual disease state in the nervous system, enabling accurate diagnosis without invasive procedures.
2Measurement precision
If diagnostic methods use invasive sample materials like cerebrospinal fluid, then diagnostic accuracy can be improved, but procedural complexity increases
Solution Approach 1:
Platelets serve as an intermediary that simplifies the diagnostic procedure. Rather than performing complex lumbar punctures to obtain cerebrospinal fluid, the method uses routine blood draws to collect platelets, which then serve as proxies for measuring neuronal pathology markers, thereby reducing procedural complexity while maintaining diagnostic accuracy.
Solution Approach 2:
The patent utilizes platelets that naturally carry biomarkers reflecting neuronal health. The body's own platelets serve the diagnostic function without requiring external intervention or complex sample preparation, enabling simple blood-based diagnosis that leverages the patient's own biological materials for self-diagnosis.
3Ease of manufacture
If protein expression levels are measured without normalization, then measurement process is simpler, but biological variation reduces reliability
Solution Approach 1:
The patent applies normalization by changing the reference parameter from absolute protein expression levels to relative expression levels compared to a reference sample. This parameter transformation (from raw intensity to normalized ratio) eliminates biological variation between individuals while preserving disease-related changes, making the measurements both simple and reliable.
Solution Approach 2:
The normalization process uses feedback from a reference sample (healthy control or baseline measurement) to adjust and correct the protein expression measurements. By comparing each sample against the reference and applying the appropriate correction factor, the method accounts for biological variation and ensures consistent, reliable results across different patients and measurement conditions.
Data Source
Figure 1
Figure 1B
Figure 2a~2b
AI summary
The present invention provides an ex vivo method for aiding the diagnosis of Alzheimer's disease in a patient, the method comprising the steps of determining the level of expression of at least four platelet proteins in a platelet sample from the patient selected from monoamine oxidase-B, coagulation factor XIIIa, total tropomyosin (α and β), WD-repeat protein 1 and apolipoprotein E4; and comparing the result of (i) to a control value, wherein a result higher than the control value is indicative of Alzheimer's disease. Preferably, the method of the invention further comprises determining the level of expression of wild-type GSTO-1 or mutant GSTO-1.