We visited an old age home named Vanaprastha Ashram, situated at Jwalapur, Haridwar, Uttarakhand. The word Vanaprastha, we noted, is the name for the third stage of life according to the traditional Hindu Varnasrama way of life. It literally translates to “journey to the forest” and signifies the stage in life where one begins to withdraw from the world and pass their social responsibilities over to the next generation. So they can completely devote themselves to spirituality in the fourth stage.

Vanaprastha Ashram is a renowned community for the elderly, focusing on living a healthy lifestyle through spirituality and meditation. But the name is also interesting because it captures the social alienation that comes with aging in our society due to the stark lack of inclusive communities and spaces for our elderly. The stories we heard there also mirrored this, particularly coupled with the effects of neurodegeneration.

Interviewing some of the residents and caregivers there was a deeply moving experience, as we witnessed firsthand their little joy in being able to interact with us meaningfully, and also how much they value their own community and practices and how important such spaces of care and support are.

We talked to Shyama Devi Ji, the caregiver of Mrs. Janaki, an 89 year old Alzheimer’s patient. Mrs. Janaki was abandoned by her son 5 years after she’d been diagnosed. Her caregiver talked about her deteriorating memory, and impulsive behavior, often leading to quarrels with neighbors. She forgets the smallest things like whether she has eaten or bathed and also who the people around her are. Her caregivers changed often because of how difficult it was to keep up with this. There was no specific medication provided to her and Shyama Ji was also beginning to find it difficult to manage her daily chores.

The conversation with Shyama Ji was an unsettling one as we empathized with her helplessness but also simultaneously recognised the urgent need for professionals better trained in geriatric care in India, particularly for dementia-afflicted patients. Despite the attempts of several experienced old-age caregivers, all of them recognised that a very specific, patient, and different approach is required to be able to support a patient with dementia.

We also talked to Rekha Ji, the wife of 85 year old Rajan Ji. She told us that 2 years ago their family met with a tragic accident when their son died, and this caused him to have a stroke which eventually turned into Alzheimer’s. Initially, she found it very difficult to manage because he could not even manage to faecate on his own. But she was grateful for the early diagnosis as now, after two years, Rajan Ji is much healthier due to proper medications and his symptoms are mild and the dementia is very manageable.

Hearing her talk about his progress and the efficacy of medicine if diagnosed in time, reaffirmed our faith in the importance of our project and refueled our drive to make the early diagnosis of Alzheimer’s an easily accessible and affordable reality.

Conversations with Alzheimer's patients and their caregivers was an enormous opportunity for growth, both for the individuals involved and for the broader community. We learnt that it’s important to approach such conversations with empathy, patience, and an understanding of the unique challenges and experiences of Alzheimer's patients and their caregivers. Listening and providing emotional support can be just as valuable as talking, as it can create a safe and open space for sharing and connection.

During the ideation of wet-lab procedures we had the opportunity of speaking with Dr. Kalyan Kumar Sadhu, Associate Professor at the Chemistry Department of IIT-Roorkee who specializes in nanobio interfacial chemistry & chemical biology, nanoparticle-DNA interaction, and the detection of biomolecules. What drew our interest to him was his work with Amyloid Beta Monomer detection in the 2020 paper, “Two instantaneous fluorogenic steps for detection of nanomolar amyloid beta monomer and its interaction with stoichiometric copper(II) ion.” At this stage we were trying to ascertain the use of Amyloid Beta as a second biomarker for our kit and discuss the forms of the peptide we should focus on.

The paper specifically focuses on the lack of detection strategies specific to Amyloid Beta Monomers in the nanomolar regions. They adopted a fluorogenic strategy where the specific fluorophore, quenched in the presence of AuNPs, is recovered in the presence of specific analytes and produces a greater fluorescence in the presence of Aβ. This also exploits the Aβ-Cu(II) complex formation.

We spoke to him at great length about the various forms Aβ is found in the body and its scope as a selective biomarker for Alzheimer’s Disease. While talking about his protocols he described the formulation of the monomers. He explained the behavior of Aβ monomers and fibrils in solution and its rate of aggregation and how we should factor that in when considering our aptamers’ selectivity to apply to the type heterogenous pool of oligomers found in saliva. We considered the need for more research into the specificities of the form of our biomarker found in saliva. This also further solidified the need for an easily scalable and adaptable tool for more convenient, cheaper clinical trials and biosensing studies. We broadened our research and literature review into studying various different reported aptamers and the form of the peptide they were specific for.

He also talked us through the various ethical and practical considerations for the use of body fluid samples in our studies and also possible future clinical trials. Their studies used Artificial Cerebrospinal Fluid and Human Serum Albumin. We discussed the specific structural hurdles faced in India in gaining permissions and making our kit a reality. However, we concluded feeling quite optimistic and motivated as he reaffirmed the need for an accessible kit like ours.

At the All India iGEM Meet, we had the opportunity to interact with several field-experts and gained valuable insight about multiple facets of our project. Prof. Debasis Nayak from IISER Bhopal, despite being very enthusiastic and motivating about our project’s direction and promise, was particularly concerned about the specificity of our biomarkers. The judges emphasized on the strict precisions required of Point-Of-Care Diagnostic Kits. Also, since our project, at that stage, was just an attempt to characterize the possible risk of developing Alzheimer’s, there were questions raised about the eventual goal of such a kit particularly when no cure exists.

This was before we had conducted several our surveys and visits to get into touch with the ground realities of our Problem Statement. With that renewed context, keeping their questions in mind the whole time, we began to reposition the entire social relevance of our project.

We conducted a more extensive literature survey about our selected biomarkers and narrowed in on exactly all the further research that needed to be done. For example, variations in quantification methods for Salivary Amyloid Beta, like the using of Mass Spectrometry would lead to non-standardised results as a mass-based quantification wouldn’t detect all different oligomers that could possibly be present. Even though reports still exist quantifying using ELISA with more reliable results, as research is still relatively nascent, such gaps can only be bridged through more extensive clinical trials. Particularly with people at earlier stages of disease progression. In the light of this, drawing inspiration from IISER TVM’s presentation and proposed implementation at AIIM, we aim to use our kit to perform these clinical trials cheaper, more easily and conveniently, to obtain and ascertain more information about our biomarkers, and possibly discover new ones, to re-design, build and improve our kit.

Second, we also realized the importance of early diagnosis regardless of the current existence of a complete ‘cure’. Early diagnosis could, in fact, make more people available for clinical trials to develop cures at a stage where they could actually be effective. Existing palliative care is also significantly more effective in delaying progression and helping management. But even apart from that, we learnt the importance of early diagnosis in helping families appropriately plan how to support and finance their loved ones and urge our healthcare to create more institutions for geriatric care.

For as long as no cure exists, it is invaluable to learn the internal happenings in your brain through a simple saliva sample, so you can make more informed decisions. And their loved ones have ample time to learn how to build a more caring and inclusive community that can support their new needs. In this context, raising awareness, interacting with stakeholders, and general Human Practices are vital parts of our project and go hand in hand with our solution to solve the problem.

iGEM IIT-Roorkee conducted an online survey to understand the awareness about Alzehimers and related Neuro-degenerative disorders among the general populace, which included students, staff and faculties. The Study would help us give an understanding regarding the future course of action to establish how fatal Alzehimers can be, if left untreated, and more dangerously untested. Our Survey got a plethora of responses from the target population, With nearly identical Male, Female responses, while a disproportionate number of students filled the form, along with working population, which helped us understand the knowledge that these employment groups possess, accordingly we could plan our workshops, and future course of action regarding the usage of our Proposed Kit.

We found out that the general knowledge about Alzheimer's is lacking with the majority of people describing their understanding between somewhat to not-very knowledgeable which shows how unaware people are about neurodegenerative disorders in general. This makes our Science and Communication aspect of the Project even more important.

Secondly, We found that people largely don’t know anyone afflicted with Alzheimer, but people do understand that Alzheimer can happen to both Younger as well as the older population which is uplifting to see as people possess scientific awareness regarding diseases.

Thirdly, we also found that people understand that Alzheimer affects the Mental and Cognitive abilities of the patient, and people are aware of challenges faced by patients in this regard.

Lastly, People appreciate increased awareness and education about Alzheimer's disease can help mitigate its impact on individuals and families as well as pitch in a need for more public awareness and advocacy efforts to address Alzheimer's disease and its impact.

This gives us a platform to build upon our awareness program among all age groups which could lead to increased usage of our Kits, helping aid the dormant patients with increased testing with an effective Kit such as ours.

As part of our collaboration with IISER Trivandrum, they visited Vithura Taluk Hospital, Thiruvananthapuram, Kerala to understand how much people understand about Alzheimer’s, raise awareness, and talk about our project. Most people very broadly described Alzheimer’s as a disease involving memory loss. People could not exactly differentiate between general memory loss because of age and Alzheimer’s, but still, when asked whether they know patients, claimed to not know many, even though they did know people with general memory loss due to age. So, we followed that question up with whether they were aware of how testing for Alzheimer’s happens currently. People responded with no, while some said by going to a doctor when someone experiences memory loss. We described how the neuropathological changes due to Alzheimer’s occur several years before the onset of clinical symptoms like memory loss and explained the invasive Cerebrospinal Fluid Testing procedure. Everyone that was interviewed agreed and understood the need for an earlier detection method as that would help them plan better and be prepared.

One of the most effective ways to indirectly access a large, well-interpreted pool of information about the demographic most affected by our problem statement is to talk to a Neurologist. The sheer amount of experience and expertise that we’re put in contact with and the wealth of information they’ve gathered over the years on a case by case basis helped us build a comprehensive understanding of the ground realities of people who actually reach the hospital for an Alzheimer’s Diagnosis.

We talked to Dr. Rajesh Patel from Jabalpur, Madhya Pradesh to gain a more scientific, and medical perspective on the populations most affected by progressive dementias.

He talked to us about the progression of Alzheimer's, its stages, and the changes he has observed in his patients gradually. He spoke about medications like memantine which slow accumulation in the brain and described their efficacy in his experience.

Then we spoke about popular diagnostic tests. The Mini-Mental State Examination (MMSE) is basically a brief 30-point questionnaire that is used to assess cognitive impairment and screen for dementia. It was first introduced by Marshal Folstein and others in 1975. The MMSE is typically administered by a healthcare professional or trained personnel and is a valuable tool for assessing cognitive function, particularly in older adults.

According to Dr. Rajesh Patel, these are the drawbacks of MMSE:

Education and Cultural Bias: The MMSE includes questions about language and mathematical abilities, which can be biased towards individuals with higher levels of education. It may not accurately assess cognitive function in people with lower educational backgrounds or from different cultural or linguistic groups. Thus failing to be an objective, inclusive test.

Sensitivity to Mild Cognitive Impairment: The MMSE may not be as sensitive in detecting mild cognitive impairment (MCI), which is a condition that falls between normal cognitive aging and dementia. MCI often requires more specialized assessments.

Inadequate for Differential Diagnosis: The MMSE is not sufficient for diagnosing specific types of dementia (e.g., Alzheimer's disease, vascular dementia) or identifying the underlying causes of cognitive impairment. Additional testing and clinical evaluation are necessary for a more accurate diagnosis.

Limited Scope: The MMSE also suffers from biases regarding what it considers to be the ‘valuable measures’ of cognitive ability. It primarily evaluates memory, attention, and language abilities. It does not assess other important cognitive functions like executive function, visuospatial skills, or complex problem-solving, which are affected in different types of dementia.

There is MRI which is very helpful in differentiating between dementia caused by Alzheimer’s to the frontal dementia and dementia caused by Parkinson’s. He told us that in Alzheimer’s Memory impairment is observed first and then behavioral changes are observed.

He also emphasized on lack of infrastructure in India and mostly those patients are neglected by family as well. He spoke about the need to increase awareness about Alzheimer's diseases and how to provide its care. Medicines combined with care can be a great weapon in fighting Alzheimers as stated by him.

We decided, accordingly, that a purely biomarker based biological POC test would be necessary for removing the subjectivity of other tests and putting easily interpretable information about the patient’s health directly in the patient’s hand. This would avoid the loopholes inevitable in subjective clinical tests informed by cultural and structural differences.

gradCapital is a pan-India student-driven institution that invests in daring student founders. It’s an institution that has funded a lot of startups all over India, and is very zealous about newer, sharper and effective ideas that students dare to think,and can be implemented.

The iGEM team had a highly productive meeting with Abhisekh SethI, the founder of GradCapital, to discuss the strategic aspects of implementing and distributing our innovative Point of Care Diagnostic Kit for Alzheimer's. We also explored market opportunities and potential scaling-up of our solution.The discussion kicked off with a comprehensive overview of the current status of our diagnostic kit. We provided insights into the technology behind our kit, emphasizing its non-invasive nature, which allows for the detection of Alzheimer's biomarkers in saliva using DNA aptamers. This breakthrough offers the potential to revolutionize the early diagnosis and management of Alzheimer's disease.

We dove into the implementation strategy, discussing the necessary steps to ensure the seamless integration of our diagnostic kit into healthcare facilities and practices. It was acknowledged that regulatory considerations, clinical trials, and partnerships with healthcare institutions would be key elements of our implementation plan.

The distribution strategy was another critical topic of discussion. We explored various distribution channels, including collaborations with medical supply companies, partnerships with pharmaceutical companies, and direct-to-consumer options. The aim was to make our diagnostic kit readily accessible to those in need, while ensuring that healthcare professionals and patients alike could easily obtain and use it.

The meeting also touched upon the potential market for our diagnostic kit. We considered the demographics of Alzheimer's patients, as well as caregivers and medical professionals, as our primary target audience. Understanding the market dynamics, such as demand, competition, and pricing strategies, will be crucial in effectively launching and promoting our kit.

Lastly, we expressed our interest in scaling up our solution to reach a broader audience. We inquired about potential investment opportunities and support from GradCapital in achieving this goal. Abhisekh Sethi shared valuable insights on fundraising, strategic partnerships, and scaling strategies.

The meeting concluded with a mutual commitment to collaborate closely in the future. We are excited about the potential of our Point of Care Diagnostic Kit for Alzheimer's and appreciate the guidance and support provided by Abhisekh in navigating the path towards successful implementation, distribution, and scalability.