Multi-analyte prognostic and diagnostic screening in blood and skin for Alzheimer's disease

Lead Research Organisation: Swansea University
Department Name: College of Engineering

Abstract

Neurodegenerative disorders are usually detected by protein biomarkers. Current conventional methods employed for diagnosing neurodegenerative disorders such as Alzheimer Disease (AD) and dementia include imaging and extraction of cerebrospinal fluid (CSF) and monitoring of biomarkers. These methods have several drawbacks which include:
1.lumbar puncture for collection of CSF from the spinal cord is an invasive treatment with potential side effects
2. screening of patients is often difficult and follow-up analysis of the same patient over several years is problematic
3. these methods are time consuming and marred by low throughput and need for specialist personnel and equipment, making it an expensive procedure to be employed for routine check-ups
4. a large increase in the number of cases every year further compounds the issue of early diagnosis and treatment

To address the above we propose the development of alternative diagnosis and screening method based on employing known biomarkers albeit in different samples matrices such as capillary blood and skin interstitial fluid. Both capillary blood and skin interstitial fluid are in constant equilibrium with venous blood. The main advantages of proposed methods include:
1.Capillary blood can be accessed using lancet whilst skin interstitial fluid can be accessed in a minimally invasive manner employing microneedle array patch
2. screening of patients for several biomarkers in simpler settings such as a Clinicians' practice or even home settings is easier, it also allows follow-up analysis over several years
3. development of low cost diagnostic kits based on capillary blood and skin interstitial fluid will facilitate early diagnosis and screening of large number of people making it an affordable procedure for healthcare systems
4. development of low cost kits based on capillary blood and skin interstitial fluid can also address the issue of large increase of numbers, globally

Technical Summary

The increase in life expectancy of the population is associated with a higher incidence of neurodegenerative diseases such as dementia.Dementia is responsible for the greatest burden of disease, with Alzheimer's disease (AD) representing over 60% to 70% of cases, worldwide. It is estimated that one in three people born today has a high probability to develop the disease thus causing a major future healthcare challenge. Both, Japan and the UK's ageing population are witnessing an increase in AD.

The main feature of neurodegenerative disorders is the deposition of misfolded proteins. Currently, the conventional methods for diagnosing AD include detection of biomarkers include PET imaging and lumbar puncture for extraction of CSF. These methods are time consuming and marred by low throughput and need for specialist personnel and equipment, making it an expensive procedure to be employed for routine check-ups. Therefore, blood-based methods for AD diagnosis are possible ways. However, as the key challenges for early diagnosis and the clinical differentiation among them, different biomarkers should be analysed simultaneously, which is not always easy. Solving the problems associated with measurement of AD biomarker in blood would help the widespread use of AD blood diagnostics, which have a high throughput and are easy to use.Our objective here is to develop multiplexed biosensing systems to demonstrate the usefulness of monitoring biomarkers in blood (capillary and venous) for early diagnosis of AD. A panel of established biomarkers (such as Ab42/40 and phosphorylated tau proteins) will be targeted for the development of the biosensing devices. This joint collaboration between academic institutions in UK and Japan brings together expertise on microneedle technology, transdermal diagnostics and biosensing technologies to develop multiplexed biosensing systems for early diagnosis and screening of Alzheimer's disease.

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