Esteemed panel of judges, respected teachers, my dear colleagues and classmates, ladies and gentlemen. Good morning!

We are group 4 of 3mt-1

and we are here to present to you our research entitled, "Accuracy of the Biomarkers Amyloid β-protein (Aβ), Total Tau (t-tau), Phosphorylated
Tau (p-tau), and Neurofilament Chain (NfL) in Diagnosing Alzheimer's Disease: A Systematic Review".

Our study aims to provide a comprehensive analysis of these four key biomarkers in early diagnosis of Alzheimer's disease, which is we know is
a significant public health concern nowadays.

Our study aims to address this problem: Detecting Alzheimer's disease (AD) at an early time is difficult without a reliable biomarker. However,
combining multiple biomarkers may improve accuracy, but their sensitivity, specificity, negative and positive predictive values, as well as the
likelihood ratio to AD need to be further studied.

Our study as mentioned earlier is of great importance since it aims to improve the diagnosis of Alzheimer's disease and patient outcomes by
creating a combination of biomarkers

The objective of study I to our compare the sensitivity, specificity, negative and positive predictive values as well as the likelihood ratio of these
biomarkers individually and in combination in a clinical setting through the use of systematic review. Our aim is accomplish this study in a 4-
month time frame.

In terms of alternative hypothesis, the researchers hypothesize that using four biomarkers together will improve the accuracy of diagnosing the
disease. On the other hand, for null hypothesis, using these biomarkers in combination will not improve diagnostic accuracy.

The RRL is categorized into different points that would prove that further research is needed with the biomarkers of AD. There are properties that
thoroughly discusses the following: what they are, where they come from, their pathophysiology and how they are as an indicator of cognitive
impairment.
The limitations is mainly concerned with the biomarkers’ limited capacity when it comes as an indicator
Lastly the gaps in literature emphasizes the small sample size, the lack of study of different combinations of other biomarkers, and the possible
changes of CSF biomarker levels when it comes to pathology.

The methodology of choice is systematic review. It is used to assess the accuracy of the four biomarkers. This includes a comprehensive search
and assessment of the quality of the included studies and a summary of the results.

The data sampling would be: database searching wherein keywords/phrases, databases used, type of study design and published date of the
studies are specified which Is also seen in the flowchart
Revman would also be utilized. it is a software designed for Systematic studies that has the capacity to eliminate or in clude studies depending on
the research problem or criteria

Now This diagram shows the search strategy and boolean operation. The search string is programmed to look for research articles that includes
specific combinations of biomarkers and terms related to their diagnostic accuracy such as specificity, sensitivity, positive predictive value, and
negative predictive value and likelihood ratio. The "OR" operator is used to group different combinations of biomarkers and terms, while the
"AND" operator is used to combine all of the groups together.

By using this search string, the researcher will be able to quickly find relevant articles. The databases used are Cochrane, Mesh, NCBI PubMed,
ResearchGate, and Semantic Scholar.

Moving on to the target population. This table presents the 4 biomarkers, their description and limitation

Beta amyloid is a protein secreted that forms insoluble plaques found in Alzheimer's disease. It is non-specific and can be found in Lewy bodies,
and Parkinson’s disease. Plasma beta amyloid has interferences as it is also bound to platelets or rbc. Phosphorylated tau is a component of
neurofibrillary tangles. It is non-specific biomarker and can also be found in other tauopathies. Total tau is a general marker of
neurodegeneration and is associated with other neurodegenerative diseases, brain injury and tissue damage. NfL is a filament released when there
is axonal damage and is associated in other types of dementia.

The eligibility criteria present certain inclusions and exclusions in this study. The participants are the patients evaluated for AD. The intervention
used are the biomarkers. The comparator are healthy adults and adults with neurodegenerative diseases other than AD. The outcomes are the
accuracy of the biomarkers. Included also are studies within the past 10 years,

For the inclusion: this study includes any case or study which evaluates biomarkers in Alzheimer's disease, preclinical Alzheimer's disease
patients, with family history of Alzheimer's, or any underlying disease which precludes the symptoms of Alzheimer's. Experimental studies on
CSF and blood-based biomarkers are also included. Studies included are based on countries with high prominence of AD cases which are listed
on the table.

In exclusion criteria we omit: any clinical trials and experimental research on treatments and drug interventions or diagnosis. Neuroanatomically,
genetically, and metabolically-detected biomarkers are also not included in this study.
There are two variable descriptions mentioned in the study, the independent and the dependent. the independent variable are the biomarkers,
while the dependent variable is the accuracy. the operational terms for accuracy, are: sensitivity and specificity, positive and negative predictive
value and likelihood ratio. All of these are clearly defined in the paper.

In processing the data Revman is used in choosing the studies which makes it unbiased.
First would be identification of the studies from the databases,
next is the screening wherein duplicates are removed,
next is eligibility which follows the criteria,
finally, the inclusion of the studies which will be analyzed for the PPV and NPV

For the analysis, NPV and PPV are applied to yield true positives, false positives, true negatives and false negatives with the disease.
A high PPV suggests that a positive biomarker test is accurate. On the other hand, a high NPV, suggests that the negative result for the biomarker
test is correct. By using this, it allows us to know the prevalence and how likely the patient has a specific disease. On the slide are formulae
tabulated needed analysis Additionally, L The Likelihood Ratio (LR) is then used to compare the probability of correctly predicted disease to the
probability of incorrectly predicted disease.

As you can see here, we have the dummy tables

In table 5 we tabulate the accuracy in terms of sensitivity and specificity of phosphorylated tau, total tau, beta amyloid, and neurofilaments with
AD and non-AD diseases
Then in table 6 we tabulate the levels of the sensitivity and specificity, PPV, NPV, and Likelihood Ratio of the combined biomarkers and identify
which combination would be the most efficient and accurate in terms of detecting AD.

The only ethical problems that arise from the study are: publication bias and transparency. This can be resolved by reporting any conflict of
interest, whether financial or non-financial, as well as including peer reviews, editor’s comment and should include complete transparency in
documentation
The expected benefits of the study are: specific and sensitive diagnosis, support for other studies, collated information and medical aid in
treatment options

Here’s our schedule

The first month involves searching for literature and screening through abstracts and titles.
The second month is for reading full texts.
A week is allocated for ethics approval,
2 weeks for data processing and encoding,
and another week for data analysis.
And for the month is dedicated in drafting the paper. The entire process will take 4 months.

Here is the tabulated budget needed for this proposal. From the start of using statistical software needed in order to retrieve data, up to the budget
needed to process the whole hard copy of the research. The total allocated budget for this study is about P7,300. Breakdowns of prices are listed
down.

That ends our presentation, we hope you appreciate our paper. To the panels, you may now raise your questions.

Esteemed panel of judges, respected teachers, my dear colleagues and classmates, ladies and gentlemen Good morning! We are group 4 of 3mt-1,
and we are here to present to you our thesis entitled, "Accuracy of the Biomarkers Amyloid--protein (A), Total Tau (t-tau), Phosphorylated Tau
(p-tau), and Neurofilament Chain (NfL) in Diagnosing Alzheimer's Disease: A Systematic Review".

Our study aims to provide a comprehensive analysis of these four key biomarkers in the early diagnosis of Alzheimer's disease, which we know is
a significant public health concern nowadays.
Our study aims to address this problem: detecting Alzheimer's disease (AD) at an early stage is difficult without a reliable biomarker. However,
combining multiple biomarkers may improve accuracy, but their sensitivity, specificity, negative and positive predictive values, as well as the
likelihood ratio to AD, need to be further studied.

Our study, as mentioned earlier, is of great importance since it aims to improve the diagnosis of Alzheimer's disease and patient outcomes by
creating a combination of biomarkers.

The objective of this study is to compare the sensitivity, specificity, negative, and predictive values as well as the likelihood ratio of these
biomarkers individually and in combination in a clinical setting through the use of a systematic review. Our aim is to accomplish this study in a 4-
month time frame.

In terms of alternative hypotheses, the researchers hypothesize that using four biomarkers together will improve the accuracy of diagnosing the
disease. On the other hand, for null hypotheses, using these biomarkers in combination will not improve diagnostic accuracy.

The RRL is categorized into different points that would prove that further research is needed with the biomarkers of AD. There are properties that
thoroughly discuss the following: what they are, where they come from, their pathophysiology, and how they are an indicator of cognitive
impairment.

The limitations are mainly concerned with the biomarkers’ limited capacity as an indicator.

Lastly, the gaps in the literature emphasize the small sample size, the lack of study of different combinations of other biomarkers, and the possible
change in CSF biomarker levels when it comes to pathology.

The methodology of choice is systematic review. It is used to assess the accuracy of the four biomarkers. This includes a comprehensive search,
an assessment of the quality of the included studies, and a summary of the results.

The data sampling would be: database searching wherein keywords or phrases, databases used, type of study design, and published date of the
studies are specified, which is also seen in the flowchart.

Revman would also be utilized. It is software designed for systematic studies to eliminate and include studies following the research question and
criteria.

Now This diagram shows the search strategy and boolean operation. The search string is programmed to look for research articles that include
specific combinations of biomarkers and terms related to their diagnostic accuracy, such as specificity, sensitivity, positive predictive value,
negative predictive value, and likelihood ratio. The "OR" operator is used to group different combinations of biomarkers and terms, while the
"AND" operator is used to combine all of the groups together.

By using this search string, the researcher will be able to quickly find relevant articles. The databases used are Cochrane, Mesh, NCBI PubMed,
ResearchGate, and Semantic Scholar.
Moving on to the target population This table presents the four biomarkers, their descriptions, and their limitations.

Beta-amyloid is a protein secreted that forms insoluble plaques found in Alzheimer's disease. It is non-specific and can be found in Lewy bodies
and Parkinson’s disease. Plasma beta amyloid has interferences as it is also bound to platelets, or RBc. Phosphorylated tau is a component of
neurofibrillary tangles. It is a non-specific biomarker and can also be found in other tauopathies. Total tau is a general marker of
neurodegeneration and is associated with other neurodegenerative diseases, brain injury, and tissue damage. NfL is a filament released when there
is axonal damage and is associated with other types of dementia.

The eligibility criteria present certain inclusions and exclusions in this study. The participants are the patients evaluated for AD. The intervention
used is the biomarker. The comparator groups are healthy adults and adults with neurodegenerative diseases other than AD. The outcomes are
both the sensitivity and specificity of the biomarkers. Studies within the past ten years will be included.

This study includes any case or study that evaluates biomarkers in Alzheimer's disease, preclinical Alzheimer's disease patients with a family
history of Alzheimer's, or any underlying disease that precludes the symptoms of Alzheimer's. Experimental studies on CSF and blood-based
biomarkers are also included. The studies included are based on countries with a high prevalence of AD cases, which are listed in the table.

In our exclusion criteria, we omit any clinical trials and experimental research on treatments, drug interventions, or diagnoses.
Neuroanatomically, genetically, and metabolically detected biomarkers are also not included in this study.

There are two variable descriptions mentioned in the study: independent and dependent. The independent variables are the biomarkers, while the
dependent variable is accuracy. The operational terms for accuracy are sensitivity and specificity, positive and negative predictive value, and
likelihood ratio. All of these are clearly defined in the paper.

In processing the data, Revman is used in choosing the studies, which makes them unbiased.

First would be the identification of the studies from the databases,

Next is the screening, wherein duplicates are removed.

Next is eligibility, which follows the criteria.

Finally, the inclusion of the studies that will be analyzed for the PPV and NPV

For the analysis, NPV and PPV are applied to yield true positives, false positives, true negatives, and false negatives for the disease.

A high PPV suggests that a positive biomarker test is accurate. On the other hand, a high NPV suggests that the negative result for the biomarker
test is correct. By using this, we can know the prevalence and how likely it is that the patient has a specific disease. On the slide are formulae
tabulated for needed analysis. Additionally, likelihood ratio (LR) is then used to compare the probability of a correctly predicted disease to the
probability of an incorrectly predicted disease.
As you can see here, we have dummy tables.

In Table 5, we tabulate the accuracy in terms of sensitivity and specificity of phosphorylated tau, total tau, beta amyloid, and neurofilaments in
AD and non-AD diseases.

Then in Table 6, we tabulate the levels of joint sensitivity and specificity, PPV, NPV, and likelihood ratio of the combined biomarkers and identify
which combination would be the most efficient and accurate in terms of detecting AD.

The only ethical problems that arise from the study are publication bias and transparency. This can be resolved by reporting any conflict of
interest, whether financial or non-financial, as well as including peer reviews, editor’s comments, and complete transparency in documentation.

The expected benefits of the study are: specific and sensitive diagnosis; support; collated information; and medical aid in treatment options.

Here’s our schedule:

The first month involves searching for literature and screening through abstracts and titles.

The second month is for reading full texts.

A week is allocated for ethics approval.

2 weeks for data processing and encoding, and another week for data analysis.

One month is dedicated to drafting the paper. The entire process will take four months.

Here is the tabulated budget needed for this proposal: From the start of using the statistical software needed in order to retrieve data, up to the
budget needed for the whole hard copy of the research, The total allocated budget for this study is about P7,300. Breakdowns of prices are listed
below.

That ends our presentation. We hope you appreciate our paper. To the panels: you may now raise your questions.