Alzheimer's Diagnosis via Circulating Nucleic Acid Detection
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Solution Overview
Problem
Current methods for diagnosing Alzheimer's disease are invasive, costly, and not suitable for early detection due to the small amount of amyloid precursor protein (APP) gene DNA in blood plasma, which is difficult to detect before the onset of dementia.
Innovation Solution
A diagnosis marker detection method that involves detecting and quantifying APP gene DNA, along with other disease-related genes like NUMB and PROK 2, from circulating nucleic acids in peripheral blood using PCR and next-generation sequencing, allowing for noninvasive and sensitive detection of Alzheimer's disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If amyloid PET is used to examine Aβ accumulation, then diagnostic accuracy is improved, but cost and invasiveness increase
Solution Approach 1:
The patent uses blood plasma as a disposable, easily obtainable sample source instead of expensive and invasive amyloid PET imaging or CSF collection. The circulating nucleic acids in blood plasma serve as a cheap alternative biomarker source that can be repeatedly sampled without significant harm or cost.
Solution Approach 2:
The patent introduces circulating nucleic acids (specifically APP gencDNA) as an intermediary biomarker that indirectly reflects Aβ accumulation and neuronal damage. This intermediary allows diagnosis without direct imaging or invasive sampling, bridging the gap between accurate diagnosis and non-invasive testing.
2Measurement precision
If CSF collection is used to measure Aβ42 and phosphorylated tau, then biomarker detection is improved, but invasiveness increases
Solution Approach 1:
The patent replaces invasive CSF collection with simple blood plasma sampling. Blood plasma is easily obtainable, can be repeatedly sampled, and contains the target biomarker (APP gencDNA) without requiring lumbar puncture or other invasive procedures.
Solution Approach 2:
Instead of collecting CSF to find biomarkers, the patent inverts the approach by collecting blood plasma and analyzing circulating nucleic acids that originate from brain tissue. This inversion allows access to brain-derived biomarkers through a peripheral, non-invasive route.
3Measurement precision
If multiple RNA types are combined as biomarkers, then diagnostic accuracy is improved, but complexity increases
Solution Approach 1:
The patent extracts and focuses on a single specific biomarker (APP gencDNA) from the complex mixture of various RNAs and proteins. By isolating this one key circulating nucleic acid marker, the patent simplifies the diagnostic test while maintaining accuracy, avoiding the need to analyze multiple different RNA types simultaneously.
Solution Approach 2:
The patent applies local quality by focusing on a specific property (circulating APP gencDNA in blood plasma) rather than analyzing all possible biomarkers. This targeted approach concentrates diagnostic power on one specific marker with known relevance to Alzheimer's disease, simplifying the overall test design.
4Ease of operation
If APP gencDNA detection is performed in blood plasma, then noninvasive diagnosis is enabled, but detection sensitivity decreases due to small amount of target
Solution Approach 1:
The patent applies preliminary action by using PCR amplification to exponentially increase the amount of APP gencDNA before detection. This pre-amplification step ensures that even trace amounts of circulating nucleic acids in blood plasma can be detected with high sensitivity, overcoming the low concentration problem.
Solution Approach 2:
The patent changes the concentration parameter of the target nucleic acid through PCR amplification. By increasing the copy number of APP gencDNA from trace levels to detectable levels, the patent maintains high detection sensitivity while using noninvasive blood plasma sampling.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables convenient, rapid, and noninvasive diagnosis of Alzheimer's disease by amplifying and analyzing specific gene sequences in blood plasma, providing early detection of neuronal damage and disease progression.
Implementation Method 1
detecting and quantifying APP gene DNA, along with other disease-related genes like NUMB and PROK 2, from circulating nucleic acids in peripheral blood using PCR
Implementation Method 2
amplifying and analyzing specific gene sequences in blood plasma, providing early detection of neuronal damage and disease progression
Data Source
AI summary
A diagnosis maker detection method comprising a disease-related gene from circulating nucleic acids (CAN) that is in peripheral blood isolated from a subject.