Molecular Tools to Detect Alloforms of Aβ and Tau: Implications for Multiplexing and Multimodal Diagnosis of Alzheimer's Disease

The advancements in the field of imaging and diagnostics have been benefitted by the concurrent expansion of molecular probes space to monitor the diverse biological targets and events. The misfolding and aggregation of amyloid beta peptide as well as Tau protein generate toxic polymorphic species (referred to as alloforms in this article) which are formally designated as core AD biomarkers by National Institute on Aging and Alzheimer's Association Research Framework (NIA-AA 2018). Positron emission tomography and magnetic resonance imaging, which are currently the efficient and sophisticated techniques in the clinical diagnosis, are incapable of detection and differentiation of various alloforms besides being not easily operable and affordable by the common people. As a consequence, fluorescence optical imaging has gained great impetus besides many recent technological advancements that have positioned its sensitivity at par with PET and MRI in addition to offering the possibility of alloform detection, rapid analyses and economic benefits to cater to a larger population. In addition, there exists an array of biomarkers or pathophysiological conditions that are known to aggravate the disease progression. This emphasises the importance of molecular tools and methods for the detection of various known as well as yet to be identified AD biomarkers. The molecular and hybrid tools intended for detection and imaging of biomarkers inside the AD brain must cross the blood brain barrier which is one of the persistent challenges for synthetic organic chemists and in this context various strategies are discussed. In this review, we have proposed multiplexed and multimodal analytical approach for the in vitro and in vivo detection and imaging of the core and indirect biomarkers in brain and bio-fluids such as cerebrospinal fluid (CSF) and blood among others to generate characteristic fingerprints to distinguish between healthy and AD patients with precision. Overall, this review offers critical discussions on design, properties, functions, advantages and limitations of the existing molecular probes besides providing current and future prospects for the development of novel diagnostic and theranostic tools for AD.