Alzheimer's disease (ad) is a prominent neurological disorder characterized by progressive brain cell death, resulting in memory loss, cognitive decline, and ultimately dementia. furthermore, a multifunctional pathway affects ad, leading to alterations at the biomolecular level as the disease advances. despite numerous diagnostic techniques, conventionally employed technology allows for the detection of ad biomarkers with high cost; low sensitivity; poor selectivity and many more. however, in recent years, bioconjugates, and receptors-based ad biomarkers recognition has shown great potential in improving the selectivity and sensitivity of ad at the molecular level. unfortunately, techniques engaged in ad core biomarker beta-amyloid1-42 (aβ1-42), tau-441, and beta (β)-site amyloid precursor protein-cleaving enzyme 1 (bace-1) detection are majorly suffering from poor sensitivity and selectivity. in this proposed work, we have particularly focused on developing an exceptionally sensitive, highly selective, cost-effective, non-invasive, label free surface plasmon resonance (spr) biosensor-based detection chip for the early-stage prognosis of alzheimer's disease (ad). therefore, in the first approach, we fabricated a graphene oxide (go) surface-decorated chitosan (cs) mediated layer-by-layer (lbl) assembly-based spr biosensor for highly sensitive and selective recognition of aβ1-42. the amine functionality of cs offers numerous sites for anti-aβ antibody immobilization, providing specific direction, high selectivity, and an adequate amount of antibody immobilization. the unique features of lbl assembly demonstrated improved selectivity towards aβ1-42 peptide, while the utilization of an affinity biotransducer with a combination of plasmonic and non-plasmonic nanomaterials enhanced sensitivity and selectivity. consequently, the linearity range and limit of detection (lod) of aβ1-42 antigens were found to be 2 - 400 ng/ml and 1.21 fg/ml, respectively. moreover, the analysis of aβ1-42 in ad-induced rats confirmed the real-time applicability of the designed spr biosensor." in the second approach, a simple, label-free, fast, highly sensitive, and selective 2d carbon backbone go patterned spr-mediated affinity biosensor was developed for tau-441 monitoring. initially, non-plasmonic nanosized go was synthesized using a modified hummers method, while green-synthesized gold nanoparticles (aunps) underwent an lbl design employing anionic and cationic polyelectrolytes. as a result, this biosensor demonstrates a broad concentration range and an impressively low detection limit, ranging from 150 ng/ml - 5 fg/ml and 13.25 fg/ml, respectively. the remarkable sensitivity of this spr biosensor stems from the combination of plasmonic aunps and non-plasmonic go. furthermore, it exhibits excellent selectivity for tau-441 in the presence of interfering molecules, which can be attributed to the immobilization of anti-tau rabbit on the surface of the lbl assembly. in the third approach, cs and sodium alginates (sa) were employed to design an lbl assembly. the cs-sa-platinum nanoparticles (pt-nps) lbl-based nanobioconjugate was utilized to decorate the carbon backbone-layered affinity spr biosensor, enabling extremely sensitive and selective sensing of bace-1. this biosensor provides a lod of 5.63 fg/ml and a wide linear range from 5 fg/ml - 150 ng/ml for bace-1 detection. additionally, selectivity and real-time analyses in spiked samples demonstrated its practical usefulness in complex specimens. the decoration of antibody-immobilized cs-sa coated pt-nps nanobioconjugate on the go surface offers various benefits, including extreme sensitivity and superb specificity. overall, this advancement could represent a safe and viable alternative to current methods. in essence, the proposed biosensor has the potential to offer a range of crucial advantages, including non-invasiveness, user-friendliness, cost-effectiveness, label-free detection, rapid results, exceptional sensitivity, and remarkable selectivity. this holistic approach holds the promise of enabling early-stage diagnosis of alzheimer's, a critical factor in improving patient outcomes and quality of life. overall, this diligent efforts in developing this spr biosensor hold the promise of addressing a pressing medical need and contributing to the broader landscape of healthcare innovation.