U1 snRNP Aggregates Detection in Neurodegenerative Disease Diagnosis

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Solution Overview

Problem

Current methods for diagnosing neurodegenerative diseases, such as Alzheimer's, lack effective tools for identifying early stages and specific protein aggregates, particularly those involving U1 small nuclear ribonucleoproteins (U1 snRNPs), which are key to understanding disease pathogenesis.

Innovation Solution

The method involves analyzing U1 snRNP components in brain tissue or cerebrospinal fluid samples for altered expression, using techniques like immunohistochemistry, mass spectrometry, and chromatography to detect U1-70K and other U1 snRNP proteins, and administering specific antibodies or antisense oligonucleotides to treat or prevent Alzheimer's disease.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current diagnostic methods are used for neurodegenerative diseases, then diagnosis can be performed, but early stages and specific protein aggregates involving U1 snRNPs cannot be effectively identified

Engineering Contradiction:
Improvedetection capabilityVSAvoiddiagnosis accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent introduces specific antibodies (e.g., anti-U1-70K antibodies) and detection reagents as intermediaries to bridge the gap between current diagnostic methods and the target protein aggregates. These intermediaries enable specific detection of U1 snRNP aggregates and other disease-related proteins that current methods cannot identify, thereby improving both measurement precision and diagnostic reliability

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs multiple detection parameters including immunohistochemistry, mass spectrometry, and chromatography to analyze U1 snRNP components. By changing and combining multiple detection parameters, the patent achieves comprehensive identification of protein aggregates and altered expression patterns, resolving the limitation of current single-parameter diagnostic methods

Inventive Principle:
Principle #35Parameter changes

2Loss of time

If U1 snRNP components are analyzed in brain tissue or CSF samples, then early diagnosis and treatment potential are enabled, but complex analytical techniques and sample manipulation are required

Engineering Contradiction:
Improvediagnosis timeVSAvoidanalysis complexity
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The patent performs preliminary actions by preparing specific antibodies, detection reagents, and control samples before actual diagnosis. Sample preprocessing steps including filtration to remove albumin and preparation of detergent-soluble and insoluble fractions are conducted in advance, enabling faster and more efficient early diagnosis while managing analytical complexity through systematic preparation

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent segments the complex analysis into distinct modules: sample preparation, detergent solubility fractionation, immunodetection of specific proteins (U1-70K, U1A, etc.), and data interpretation. This segmentation allows each step to be optimized independently and facilitates early diagnosis by making the overall complex process more manageable and systematic

Inventive Principle:
Principle #1Segmentation

3Object-generated harmful factors

If specific antibodies or antisense oligonucleotides are administered to treat Alzheimer's, then potential treatment and prevention are achieved, but targeted delivery and specificity challenges arise

Engineering Contradiction:
Improvedisease pathologyVSAvoidtreatment delivery
Core Design Contradiction:
Object-generated harmful factorsVSEase of manufacture

Solution Approach 1:

The patent uses antibodies and antisense oligonucleotides as intermediaries to deliver therapeutic effects. These biologics specifically bind to target proteins or RNA sequences involved in Alzheimer's pathogenesis, enabling targeted treatment while minimizing off-target effects. The intermediaries bridge the gap between administration and therapeutic action despite delivery challenges

Inventive Principle:
Principle #24Intermediary (Mediator)

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

This approach enables early diagnosis and potential treatment of Alzheimer's by identifying U1 snRNP aggregates and altering their expression, thereby addressing the underlying RNA splicing defects and amyloid precursor protein regulation.

Implementation Method 1

analyzing U1 snRNP components in brain tissue or cerebrospinal fluid samples for altered expression, using techniques like immunohistochemistry

Methodology Applied
Scientific EffectAntibody-antigen binding:

Implementation Method 2

using techniques like immunohistochemistry, mass spectrometry, and chromatography to detect U1-70K and other U1 snRNP proteins

Methodology Applied
Scientific EffectMass spectrometry:

Implementation Method 3

using techniques like immunohistochemistry, mass spectrometry, and chromatography to detect U1-70K and other U1 snRNP proteins

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentUS9758809B2RNA splicing alterations and U1 small nuclear ribonucleoproteins in neurodegenerative diseases
Publication Date: 2017.09.12 EMORY UNIVERSITY
  • US9758809B2 patent drawing
  • US9758809B2 patent drawing
  • US9758809B2 patent drawing

AI summary

This disclosure relates to methods of diagnosing neurodegenerative disease by analyzing proteins or protein expression profiles in a subject, or RNA or RNA expression profiles in a subject. In certain embodiments, the disclosure contemplates the diagnosis of preclinical or symptomatic stages of Alzheimer's disease, mild cognitive impairment, or chronic traumatic encephalopathy by identification of components of U1 small nuclear ribonucleoproteins or fragments thereof which are capable of forming cytoplasmic tangle-like structures.