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
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.
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.
Related Projects
| Project Reference | Relationship | Related To | Start | End | Award Value |
|---|---|---|---|---|---|
| MR/X02153X/1 | 07/02/2023 | 30/05/2024 | £608,594 | ||
| MR/X02153X/2 | Transfer | MR/X02153X/1 | 31/05/2024 | 06/02/2026 | £393,943 |
| Description | MRC- AMED (UK Japan) Bi-lateral or Multi-lateral Partnerships |
| Organisation | Imperial College London |
| Department | Department of Chemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Our UK research team has played a crucial role in the collaboration, making tangible contributions that have advanced the project's objectives. For instance, during Dr. Sanjiv Sharma (SS) 's visit to Tokyo University of Agriculture and Technology (TUAT) and the National Institutes for Quantum Science and Technology (QST) in June 2023, knowledge exchange sessions were conducted, where expertise in microdialysis and microneedle technology was shared. The joint experiment sessions at Murakami-San's lab at TUAT's Fuchu campus, led to the transfer of essential technology information critical for our research, particularly in correlation studies of biomarkers of Alzheimer's Disease between venous blood, capillary blood, and the skin compartment in mouse models. SS also gave a seminar at the QST on "Subdermal wearable biosensors". Furthermore, material transfer has been a significant aspect of our collaboration. Dr. Daimei Miura successfully prepared novel antibodies against amyloid peptides, which were transferred to Swansea University. These antibodies have been pivotal in the development of biosensing devices by Dr. Arjun Ajith Mohan. Notably, Dr. Mohan's progress in developing biosensors for tau441 proteins, utilizing the materials provided by our Japanese partners, has been commendable. It is evidenced by the imminent manuscript submission detailing his advancements, scheduled for publication in the coming months. Additionally, reciprocal visits have facilitated direct interaction and knowledge exchange between partner institutions. Damei Miura from TUAT spent time at Swansea University in November 2023, further enhancing collaborative efforts. These visits have strengthened our partnership and fostered cross-pollination of ideas and expertise, ultimately driving forward the research objectives outlined in the MRC AMED grant. Overall, our team's contributions, supported by specific examples and evidence such as dates and outcomes, have been instrumental in advancing the collaboration and achieving significant progress towards our shared goals in Alzheimer's Disease research and diagnostics. |
| Collaborator Contribution | Our partners from Japan have made substantial contributions to the collaboration, enriching the project with their expertise and resources. Tokyo University of Agriculture and Technology (TUAT) and the National Institutes for Quantum Science and Technology (QST) have been instrumental in advancing our research objectives through various initiatives. For instance, during Dr. Sanjiv Sharma's (SS) visit to TUAT and QST in June 2023, our Japanese partners hosted SS and actively engaged in knowledge exchange sessions focused on bioreceptor technology. These sessions facilitated the transfer of essential technology information critical for our research, particularly in correlation studies of biomarkers of Alzheimer's Disease between venous blood, capillary blood, and the skin compartment in mouse models. Moreover, TUAT has contributed significantly to the collaboration through material transfer. Dr. Daimei Miura successfully prepared novel antibodies against amyloid peptides, which were transferred to Swansea University. These antibodies have been pivotal in the development of biosensing devices by our team, led by Dr. Arjun Ajith Mohan. Notably, Dr. Mohan's progress in developing biosensors for amyloid and tau441 proteins, utilising the materials provided by TUAT, has been commendable. It is evidenced by the imminent manuscript submission detailing his advancements, scheduled for publication in the coming months. Furthermore, reciprocal visits have facilitated direct interaction and knowledge exchange between partner institutions. Damei Miura from TUAT spent time at Swansea University in November 2023, further enhancing collaborative efforts. These visits have strengthened our partnership and fostered cross-pollination of ideas and expertise, ultimately driving forward the research objectives outlined in the MRC AMED grant. Overall, our partners' contributions, supported by specific examples and dates, have been integral to the success of the collaboration, underscoring the significance of our collective efforts in advancing Alzheimer's Disease research and diagnostics. |
| Impact | 1. Ms. Beth Norman presented a poster on " Bloodless Diagnostics for Neurodegenerative Diseases" at the BioMedEng 2023 at Swansea University 2. Dr Arjun Ajith Mohan (Swansea University, UK) 's abstract titled "Towards point-of-care diagnostics for early detection of Alzheimer's Disease" accepted for presentation at 8th International Conference on Bio-Sensing Technology, 12-15 May 2024 | Seville, Spain 3. Dr Arjun Ajith Mohan (Swansea University, UK) 's submitted manuscript "Towards CSF-free ultra sensitive Alzheimer's diagnostics using MIPS" to IEEE Biosensors for publication and presentation at IEEE Biosensors 2024 at C Cambridge, UK |
| Start Year | 2023 |
| Description | MRC- AMED (UK Japan) Bi-lateral or Multi-lateral Partnerships |
| Organisation | National Institutes for Quantum and Radiological Science and Technology |
| Country | Japan |
| Sector | Public |
| PI Contribution | Our UK research team has played a crucial role in the collaboration, making tangible contributions that have advanced the project's objectives. For instance, during Dr. Sanjiv Sharma (SS) 's visit to Tokyo University of Agriculture and Technology (TUAT) and the National Institutes for Quantum Science and Technology (QST) in June 2023, knowledge exchange sessions were conducted, where expertise in microdialysis and microneedle technology was shared. The joint experiment sessions at Murakami-San's lab at TUAT's Fuchu campus, led to the transfer of essential technology information critical for our research, particularly in correlation studies of biomarkers of Alzheimer's Disease between venous blood, capillary blood, and the skin compartment in mouse models. SS also gave a seminar at the QST on "Subdermal wearable biosensors". Furthermore, material transfer has been a significant aspect of our collaboration. Dr. Daimei Miura successfully prepared novel antibodies against amyloid peptides, which were transferred to Swansea University. These antibodies have been pivotal in the development of biosensing devices by Dr. Arjun Ajith Mohan. Notably, Dr. Mohan's progress in developing biosensors for tau441 proteins, utilizing the materials provided by our Japanese partners, has been commendable. It is evidenced by the imminent manuscript submission detailing his advancements, scheduled for publication in the coming months. Additionally, reciprocal visits have facilitated direct interaction and knowledge exchange between partner institutions. Damei Miura from TUAT spent time at Swansea University in November 2023, further enhancing collaborative efforts. These visits have strengthened our partnership and fostered cross-pollination of ideas and expertise, ultimately driving forward the research objectives outlined in the MRC AMED grant. Overall, our team's contributions, supported by specific examples and evidence such as dates and outcomes, have been instrumental in advancing the collaboration and achieving significant progress towards our shared goals in Alzheimer's Disease research and diagnostics. |
| Collaborator Contribution | Our partners from Japan have made substantial contributions to the collaboration, enriching the project with their expertise and resources. Tokyo University of Agriculture and Technology (TUAT) and the National Institutes for Quantum Science and Technology (QST) have been instrumental in advancing our research objectives through various initiatives. For instance, during Dr. Sanjiv Sharma's (SS) visit to TUAT and QST in June 2023, our Japanese partners hosted SS and actively engaged in knowledge exchange sessions focused on bioreceptor technology. These sessions facilitated the transfer of essential technology information critical for our research, particularly in correlation studies of biomarkers of Alzheimer's Disease between venous blood, capillary blood, and the skin compartment in mouse models. Moreover, TUAT has contributed significantly to the collaboration through material transfer. Dr. Daimei Miura successfully prepared novel antibodies against amyloid peptides, which were transferred to Swansea University. These antibodies have been pivotal in the development of biosensing devices by our team, led by Dr. Arjun Ajith Mohan. Notably, Dr. Mohan's progress in developing biosensors for amyloid and tau441 proteins, utilising the materials provided by TUAT, has been commendable. It is evidenced by the imminent manuscript submission detailing his advancements, scheduled for publication in the coming months. Furthermore, reciprocal visits have facilitated direct interaction and knowledge exchange between partner institutions. Damei Miura from TUAT spent time at Swansea University in November 2023, further enhancing collaborative efforts. These visits have strengthened our partnership and fostered cross-pollination of ideas and expertise, ultimately driving forward the research objectives outlined in the MRC AMED grant. Overall, our partners' contributions, supported by specific examples and dates, have been integral to the success of the collaboration, underscoring the significance of our collective efforts in advancing Alzheimer's Disease research and diagnostics. |
| Impact | 1. Ms. Beth Norman presented a poster on " Bloodless Diagnostics for Neurodegenerative Diseases" at the BioMedEng 2023 at Swansea University 2. Dr Arjun Ajith Mohan (Swansea University, UK) 's abstract titled "Towards point-of-care diagnostics for early detection of Alzheimer's Disease" accepted for presentation at 8th International Conference on Bio-Sensing Technology, 12-15 May 2024 | Seville, Spain 3. Dr Arjun Ajith Mohan (Swansea University, UK) 's submitted manuscript "Towards CSF-free ultra sensitive Alzheimer's diagnostics using MIPS" to IEEE Biosensors for publication and presentation at IEEE Biosensors 2024 at C Cambridge, UK |
| Start Year | 2023 |
| Description | MRC- AMED (UK Japan) Bi-lateral or Multi-lateral Partnerships |
| Organisation | Tokyo University of Agriculture and Technology |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Our UK research team has played a crucial role in the collaboration, making tangible contributions that have advanced the project's objectives. For instance, during Dr. Sanjiv Sharma (SS) 's visit to Tokyo University of Agriculture and Technology (TUAT) and the National Institutes for Quantum Science and Technology (QST) in June 2023, knowledge exchange sessions were conducted, where expertise in microdialysis and microneedle technology was shared. The joint experiment sessions at Murakami-San's lab at TUAT's Fuchu campus, led to the transfer of essential technology information critical for our research, particularly in correlation studies of biomarkers of Alzheimer's Disease between venous blood, capillary blood, and the skin compartment in mouse models. SS also gave a seminar at the QST on "Subdermal wearable biosensors". Furthermore, material transfer has been a significant aspect of our collaboration. Dr. Daimei Miura successfully prepared novel antibodies against amyloid peptides, which were transferred to Swansea University. These antibodies have been pivotal in the development of biosensing devices by Dr. Arjun Ajith Mohan. Notably, Dr. Mohan's progress in developing biosensors for tau441 proteins, utilizing the materials provided by our Japanese partners, has been commendable. It is evidenced by the imminent manuscript submission detailing his advancements, scheduled for publication in the coming months. Additionally, reciprocal visits have facilitated direct interaction and knowledge exchange between partner institutions. Damei Miura from TUAT spent time at Swansea University in November 2023, further enhancing collaborative efforts. These visits have strengthened our partnership and fostered cross-pollination of ideas and expertise, ultimately driving forward the research objectives outlined in the MRC AMED grant. Overall, our team's contributions, supported by specific examples and evidence such as dates and outcomes, have been instrumental in advancing the collaboration and achieving significant progress towards our shared goals in Alzheimer's Disease research and diagnostics. |
| Collaborator Contribution | Our partners from Japan have made substantial contributions to the collaboration, enriching the project with their expertise and resources. Tokyo University of Agriculture and Technology (TUAT) and the National Institutes for Quantum Science and Technology (QST) have been instrumental in advancing our research objectives through various initiatives. For instance, during Dr. Sanjiv Sharma's (SS) visit to TUAT and QST in June 2023, our Japanese partners hosted SS and actively engaged in knowledge exchange sessions focused on bioreceptor technology. These sessions facilitated the transfer of essential technology information critical for our research, particularly in correlation studies of biomarkers of Alzheimer's Disease between venous blood, capillary blood, and the skin compartment in mouse models. Moreover, TUAT has contributed significantly to the collaboration through material transfer. Dr. Daimei Miura successfully prepared novel antibodies against amyloid peptides, which were transferred to Swansea University. These antibodies have been pivotal in the development of biosensing devices by our team, led by Dr. Arjun Ajith Mohan. Notably, Dr. Mohan's progress in developing biosensors for amyloid and tau441 proteins, utilising the materials provided by TUAT, has been commendable. It is evidenced by the imminent manuscript submission detailing his advancements, scheduled for publication in the coming months. Furthermore, reciprocal visits have facilitated direct interaction and knowledge exchange between partner institutions. Damei Miura from TUAT spent time at Swansea University in November 2023, further enhancing collaborative efforts. These visits have strengthened our partnership and fostered cross-pollination of ideas and expertise, ultimately driving forward the research objectives outlined in the MRC AMED grant. Overall, our partners' contributions, supported by specific examples and dates, have been integral to the success of the collaboration, underscoring the significance of our collective efforts in advancing Alzheimer's Disease research and diagnostics. |
| Impact | 1. Ms. Beth Norman presented a poster on " Bloodless Diagnostics for Neurodegenerative Diseases" at the BioMedEng 2023 at Swansea University 2. Dr Arjun Ajith Mohan (Swansea University, UK) 's abstract titled "Towards point-of-care diagnostics for early detection of Alzheimer's Disease" accepted for presentation at 8th International Conference on Bio-Sensing Technology, 12-15 May 2024 | Seville, Spain 3. Dr Arjun Ajith Mohan (Swansea University, UK) 's submitted manuscript "Towards CSF-free ultra sensitive Alzheimer's diagnostics using MIPS" to IEEE Biosensors for publication and presentation at IEEE Biosensors 2024 at C Cambridge, UK |
| Start Year | 2023 |
| Description | MRC- AMED (UK Japan) Bi-lateral or Multi-lateral Partnerships |
| Organisation | University of Glasgow |
| Department | School of Engineering Glasgow |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Our UK research team has played a crucial role in the collaboration, making tangible contributions that have advanced the project's objectives. For instance, during Dr. Sanjiv Sharma (SS) 's visit to Tokyo University of Agriculture and Technology (TUAT) and the National Institutes for Quantum Science and Technology (QST) in June 2023, knowledge exchange sessions were conducted, where expertise in microdialysis and microneedle technology was shared. The joint experiment sessions at Murakami-San's lab at TUAT's Fuchu campus, led to the transfer of essential technology information critical for our research, particularly in correlation studies of biomarkers of Alzheimer's Disease between venous blood, capillary blood, and the skin compartment in mouse models. SS also gave a seminar at the QST on "Subdermal wearable biosensors". Furthermore, material transfer has been a significant aspect of our collaboration. Dr. Daimei Miura successfully prepared novel antibodies against amyloid peptides, which were transferred to Swansea University. These antibodies have been pivotal in the development of biosensing devices by Dr. Arjun Ajith Mohan. Notably, Dr. Mohan's progress in developing biosensors for tau441 proteins, utilizing the materials provided by our Japanese partners, has been commendable. It is evidenced by the imminent manuscript submission detailing his advancements, scheduled for publication in the coming months. Additionally, reciprocal visits have facilitated direct interaction and knowledge exchange between partner institutions. Damei Miura from TUAT spent time at Swansea University in November 2023, further enhancing collaborative efforts. These visits have strengthened our partnership and fostered cross-pollination of ideas and expertise, ultimately driving forward the research objectives outlined in the MRC AMED grant. Overall, our team's contributions, supported by specific examples and evidence such as dates and outcomes, have been instrumental in advancing the collaboration and achieving significant progress towards our shared goals in Alzheimer's Disease research and diagnostics. |
| Collaborator Contribution | Our partners from Japan have made substantial contributions to the collaboration, enriching the project with their expertise and resources. Tokyo University of Agriculture and Technology (TUAT) and the National Institutes for Quantum Science and Technology (QST) have been instrumental in advancing our research objectives through various initiatives. For instance, during Dr. Sanjiv Sharma's (SS) visit to TUAT and QST in June 2023, our Japanese partners hosted SS and actively engaged in knowledge exchange sessions focused on bioreceptor technology. These sessions facilitated the transfer of essential technology information critical for our research, particularly in correlation studies of biomarkers of Alzheimer's Disease between venous blood, capillary blood, and the skin compartment in mouse models. Moreover, TUAT has contributed significantly to the collaboration through material transfer. Dr. Daimei Miura successfully prepared novel antibodies against amyloid peptides, which were transferred to Swansea University. These antibodies have been pivotal in the development of biosensing devices by our team, led by Dr. Arjun Ajith Mohan. Notably, Dr. Mohan's progress in developing biosensors for amyloid and tau441 proteins, utilising the materials provided by TUAT, has been commendable. It is evidenced by the imminent manuscript submission detailing his advancements, scheduled for publication in the coming months. Furthermore, reciprocal visits have facilitated direct interaction and knowledge exchange between partner institutions. Damei Miura from TUAT spent time at Swansea University in November 2023, further enhancing collaborative efforts. These visits have strengthened our partnership and fostered cross-pollination of ideas and expertise, ultimately driving forward the research objectives outlined in the MRC AMED grant. Overall, our partners' contributions, supported by specific examples and dates, have been integral to the success of the collaboration, underscoring the significance of our collective efforts in advancing Alzheimer's Disease research and diagnostics. |
| Impact | 1. Ms. Beth Norman presented a poster on " Bloodless Diagnostics for Neurodegenerative Diseases" at the BioMedEng 2023 at Swansea University 2. Dr Arjun Ajith Mohan (Swansea University, UK) 's abstract titled "Towards point-of-care diagnostics for early detection of Alzheimer's Disease" accepted for presentation at 8th International Conference on Bio-Sensing Technology, 12-15 May 2024 | Seville, Spain 3. Dr Arjun Ajith Mohan (Swansea University, UK) 's submitted manuscript "Towards CSF-free ultra sensitive Alzheimer's diagnostics using MIPS" to IEEE Biosensors for publication and presentation at IEEE Biosensors 2024 at C Cambridge, UK |
| Start Year | 2023 |