Simple Saliva based test for Alzheimer disease


Background


An Epidemic plagues 50 million people worldwide and is one of the leading causes of death.The modern Epidemic is Alzheimer disease(AD). 1 in 4 AD patients are not diagnosed.The vulnerable age is largely above 60 but considering the fact that the development of disease begins 5-10 years symptoms it could also include in the age group of 30-50 age group.Approximately there are 200,000 individuals under age 65 who have younger-onset Alzheimer's and also adults who are at risk of AD

There exists no cure for the disease and the current treatment is palliative in nature.There exists no treatment as we had been dogmatic in approach towards the disease.Another facet to the epidemic is the inaccurate and late diagnosis of the disease.disease.Current diagnosis involves

cognitive tests and expensive imaging test which are imprecise.


The key to cure the disease is to prevent the disease.Diagnosis of the disease in the pre-symptomatic phrase coupled with a personalised medicine can help us prevent the disease.We had been working upon a simple saliva based test for the Alzheimer disease.It detects the disease 5-10 years before onset of disease.The test enables us to discern the disease from other neurodegenerative disease which lead to dementia enabling an accurate treatment.



Our Goals




1)Our Research seeks to develop a simple saliva based test for AD which detects Aβ 42 in saliva which is elevated in pre-AD,MCI and AD patients. Interestingly,the levels of the biomarker were elevated in patients with PS-1 mutation which further validate our finding.


2).Our research broadly focuses on 2 aspects the former is development of bioimpedance sensor using f-EIS and the latter being development of a microcontroller to measure impedance.The sensor and the device can be connected by a a cable connector (DRP-CAC, Metrohm)


3)For developing the biosensor exploiting microfluidics could be a better choice for developing the detection system. An enhanced detection system based on a simple, electroanalytical system—based on the combination of a microcontroller impedance meter with easily fabricated Micro-Paper-based Analytical Devices (μPADs). This is coupled with Faradaic electrochemical impedance spectroscopy (f-EIS) in the presence of redox reagent, e.g., [Fe(CN)6] 3−/4−, is used in biosensor owing to its high sensitivity.The study aims at developing the sensor on these lines and testing this against electrochemical analyser(CHI660E (CH instruments, USA) electrochemical analyzer)


4)After developing the biosensor,a portable EIS onboard microcontroller for performing EIS and standardising this device against the electrochemical analyser.We anticipate the initial test shall be semi-quantitative.


5)After developing this MVP,We would like to further optimise the device Optimisation would include utilising aptamers, improving on the impedance detection device(integrating with smartphone etc) ,further miniaturizing the device.





Why is this project Important?



The progression of Alzheimer’s disease can be broken down into three general stages: preclinical, mild cognitive impairment, and dementia.Preclinical Alzheimer’s disease describes a person who has no cognitive symptoms, but has signs of pathology on brain imaging or blood/cerebrospinal fluid (CSF) biomarkers.The brain imaging test and CSF is often cumbersome and expensive.The need of the hour is a test which can be integrated into routine healthcare checkups.The characteristics of the test should be-


1)Satisfy the ASSURED criteria by WHO

2)enable Point of care(POC) testing.Further optimisation would make the test viable in a home setting.

3)distinguish between Alzheimer and other neurodegenerative disease


The saliva based test developed by Speaking Callosum satisfy above parameters and enable diagnosis of the disease in Pre-AD/MCI stage.This would enable us to prevent the disease with suitable therapeutic intervention.It has been demonstrated that NSAID (nonsteroidal anti-inflammatory drug) particularly ibuprofen when administered in early stages prevent the disease.Naman Rai had been working on a cobalamin(B12) therapy for Alzheimer disease.B12 has therapeutic implications owing to anti-inflammatory,anti-oxidant,neuroprotective and its role in epigenetic regulation.High levels of B12 reduce homocysteine as Vitamin B12 (cobalamin) plays a vital role in the conversion of homocysteine to methionine in methionine cycle.These therapies coupled up with other therapies may prevent Alzheimer disease.


Also the technology developed(i.e-Biosensor coupled with impedance measuring microcontroller) can be extrapolated to any disease.This is made possible by changing the biomarker being detected and slight modification in microfluidic device(chemical functionalization) and in the onboard portable impedance measuring microcontroller.This promise to revolutionise medical diagnostics and make POC testing more sensitive and specific.


Value Proposition


1)Pioneers in the field of saliva testing for Alzheimer disease.It detects the disease 5-10 years before onset of the disease.


2)It satisfies the ASSURED CRITERIA by WHO.


3)Multidisciplinary approach towards the disease


4)The device enables POC testing in home setting


5)Distinguish between Alzheimer and other neurodegenerative disease


Potential Outcomes

1)A saliva based test for Alzheimer disease which can be integrated into routine healthcare checkups which enable us to screen large sections of population.For instance. 1 in 4 AD patients are not diagnosed.The age is largely above 60 but considering the fact that the development of disease begins 5-10 years symptoms it could also include in the age group of 30-50 age group.Approximately there are 200,000 individuals under age 65 who have younger-onset Alzheimer's and also adults who are at risk of Alzheimer.





2)Extrapolate the technology to the diagnosis of other diseases like various type of cancer,parkinson’s disease(i.e-other neurodegenerative disease) and other infectious diseases like COVID-19,HIV etc.