Plasma Biomarker Detection for Alzheimer's Diagnosis

Solution Overview

Problem

Current diagnostic tools for Alzheimer's Disease (AD) are inadequate, lacking effective early detection methods, with existing methods being expensive, invasive, and not specifically indicative of AD, leading to treatments being implemented after significant neuronal damage has occurred.

Innovation Solution

Development of compositions and methods involving the measurement of plasma levels of activated factor XII (FXII) and cleaved high molecular weight kininogen (HK) to aid in AD diagnosis, utilizing specific antibodies and assays like ELISA to detect HK and its cleaved form (HKc) as biomarkers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If brain imaging or cerebrospinal fluid analysis is used for early AD detection, then diagnostic accuracy is improved, but cost and invasiveness increase

Engineering Contradiction:

Improvediagnostic accuracyVSAvoidinvasiveness

Core Design Contradiction:

Measurement precisionVSEase of operation

Solution Approach 1:

The patent employs a disposable, minimally invasive plasma blood test that detects AD biomarkers (FXIIa and HKc) without requiring expensive, specialized equipment or invasive procedures. This single-use diagnostic approach provides early detection capability at low cost and with minimal patient burden, resolving the contradiction between diagnostic accuracy and ease of operation

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent uses plasma as an intermediary fluid that reflects brain pathology without requiring direct brain sampling. By detecting FXIIa and HKc levels in peripheral plasma, the test indirectly measures AD-related changes in the brain, achieving accurate early detection through a non-invasive blood draw rather than invasive cerebrospinal fluid analysis or expensive imaging

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If brain imaging or CSF analysis is used for early AD detection, then diagnostic capability is improved, but cost increases

Engineering Contradiction:

Improveearly detection capabilityVSAvoidcost

Core Design Contradiction:

Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent employs a disposable, minimally invasive plasma blood test that detects AD biomarkers (FXIIa and HKc) without requiring expensive, specialized equipment or invasive procedures. This single-use diagnostic approach provides early detection capability at low cost and with minimal patient burden, resolving the contradiction between diagnostic accuracy and ease of operation

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent creates a simplified copy of the diagnostic information by measuring plasma biomarkers that mirror brain pathology. Instead of directly imaging or analyzing cerebrospinal fluid, the test uses a plasma surrogate that contains reflective biomarkers of AD, providing equivalent early detection information at a fraction of the cost through standard blood draw and ELISA methodology

Inventive Principle:

Principle #26Copying

3Ease of operation

If cognitive decline-based diagnosis is used, then diagnostic simplicity is improved, but timing of detection worsens

Engineering Contradiction:

Improvediagnostic simplicityVSAvoiddetection timing

Core Design Contradiction:

Ease of operationVSLoss of time

Solution Approach 1:

The patent measures plasma FXIIa and HKc levels as preliminary biomarkers that indicate AD pathology before significant cognitive decline occurs. By detecting these biomarkers in plasma, the test performs preliminary detection of disease presence and activity, enabling intervention before the irreversible neuronal damage and cognitive symptoms that characterize later AD stages

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses plasma as an intermediary fluid that reflects brain pathology without requiring direct brain sampling. By detecting FXIIa and HKc levels in peripheral plasma, the test indirectly measures AD-related changes in the brain, achieving accurate early detection through a non-invasive blood draw rather than invasive cerebrospinal fluid analysis or expensive imaging

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

Provides a sensitive and minimally invasive tool for early AD diagnosis, allowing for potential treatment at earlier stages before irreversible neuronal damage, using plasma samples and specific antibodies to quantify HK and HKc levels.

Implementation Method 1

utilizing specific antibodies and assays like ELISA to detect HK and its cleaved form (HKc) as biomarkers

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 2

assays like ELISA to detect HK and its cleaved form (HKc) as biomarkers

Methodology Applied

Scientific EffectELISA:

Data Source

PatentUS10295550B2Compositions and methods for use in diagnosis of alzheimer's disease

Publication Date: 2019.05.21 THE ROCKEFELLER UNIV

AI summary

Provided are compositions and methods useful in the diagnosis of Alzheimer's Disease (AD). The methods involve immunologically testing biological samples for an amount of high molecular weight kininogen (HK) and cleaved high molecular weight kininogen (HKc), wherein determining less HK relative to a normal control, or determining more HKc relative to a normal control, or a combination thereof, aids in diagnosis of AD. Hybridomas and monoclonal antibodies bind with specificity to either HK alone, or to both HK and HKc. Kits for use in immunological AD testing using the mAbs are also provided.