Accuracy of the biomarkers amyloid p-protein (ap), total tau (t-tau), phosphorylated tau (p-tau), and neurofilament chain (NFL) in diagnosing ALZHEIMER'S disease: a systematic review [author]: Angon, Rosh Matthew R., Baetiong, Kai Irish D., Del Rosario, Hannah Sophia D.S., Maningding, Jereez Xean J. Manuel, Dainty Jewel C., Mercado, Romulo III D., Quizana, Jezzel Mae G., Santiago, Stephanie Marie G. Saren, Rain Stephanie I., Viray, Jessica Chelsea S.

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ABSTRACT:
Early detection of Alzheimer's Disease was challenging due to the lack of reliable biomarkers detect the disease before the onset of symptoms. The study aimed to systematically compare the individual and combined performance, in terms of sensitivity and specificity, of the biomarkers, namely amyloid beta protein (A3), total tau (t-tau), phosphorylated tau (p-tau) and
neurofilament chain (Nfl) in the clinical setting as these are the commonly used hallmarks, except NFL which is new, for diagnosis of AD. The search for scholarly articles was guided by the PRISMA Framework. The risk of bias assessment complied with the Q. UADAS-2 Checklist and that can STATA was used for the forest plot. Of 142 studies initially identified from the databases, 44 studies made it through the quality evaluation. ELISA was the method of detection used by most studies. All individual and combined biomarkers had good to excellent discriminatory ability to diagnose patients with and without AD except for t-tau + NFL. Individually, p-tau is the most reliable biomarker with the highest value of 86 (95% Cl) and the lowest I2 with 63.8 which exhibits low heterogeneity. Among the combinations of biomarkers, the most promising is p-tau + beta amyloid, with an AUC of 92. However, moderate to high heterogeneity together with long ranges of specificity and sensitivity was present in the biomarker’s subgroup, possibly due to the lack of subgroup analysis and by different contexts such as the different use of samples, methodologies and modalities against the reference articles. The findings highlighted the
potential of biomarker combinations to improve the accuracy of diagnosis and risk prediction for the disease but the issue of heterogeneity requires more attention.
KEYWORDS: Alzheimer's Disease (AD), biomarkers, sensitivity\ specificity.

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