Metal–Organic Frameworks as Interfacial Platforms for Early Diagnosis of Alzheimer’s Disease

Alzheimer's disease (AD), a progressive and debilitating neurodegenerative disorder, continues to pose a formidable challenge in medical science due to its intricate pathophysiology, delayed diagnosis, and the persistent absence of curative therapies. Although significant strides have been made in elucidating its underlying molecular mechanisms, conventional diagnostic modalities, including cerebrospinal fluid (CSF) analysis, positron emission tomography (PET), and magnetic resonance imaging (MRI), remain hindered by invasiveness, prohibitive costs, and inadequate sensitivity during the early stages of the disease. In response to these limitations, this review delves into the emerging potential of metal-organic frameworks (MOFs) as a next-generation solution for AD diagnostics and therapeutics. Owing to their high porosity, extensive surface area, and customizable architecture, MOFs offer a versatile platform for biosensing applications, particularly for the ultrasensitive detection of hallmark AD biomarkers such as amyloid-β (Aβ) peptides and hyperphosphorylated tau proteins. Particularly, the focus has been on the incorporation of biologically relevant metals, zinc, copper, iron, and aluminum, whose dysregulation has been connected to the AD pathology. Electrochemiluminescence resonance energy transfer (ECL-RET) platforms, dual-signal immunosensors, and aptasensors are currently the most cutting-edge MOF-based technologies, which have also demonstrated femtomolar-level sensitivity and operational robustness when tested with complicated biological systems. MOFs, in contrast to traditional inorganic nanomaterials, are superior due to traits such as biocompatibility and biodegradability. Moreover, in therapeutic domains, they serve as carriers for targeted drug delivery and controlled release systems. Parallelly, incorporation of MOF-based biosensors into the point-of-care (POC) devices facilitates noninvasive and rapid screening in primary care and decentralized settings, which is crucial in a disease like AD. Collectively, MOF-based biosensors represent a paradigm shift in AD diagnostics, offering a path toward precision medicine.