Metal-organic frameworks (MOFs) have emerged as highly porous/crystalline materials prepared from metal ions/clusters and organic ligands [[1], [2], [3], [4], [5], [6], [7], [8], [9]], which have attracted the biomedical area due to their extraordinary chemical and physical attributes such as high porosity, large surface area, tailorable pore size/structure, versatile modifications, and biocompatibility [[10], [11], [12], [13], [14], [15]]. These properties make MOFs as potential candidates for drug delivery, biosensing, nanothermometry, magnetic resonance imaging (MRI) contrast agents, and bioimaging (Fig. 1). The growing applications of MOFs in gas storage/separation, organic dye adsorption, heavy metal removal, catalysts, energy storage, and sensors [16,17] have further made them attractive materials in biomedical applications in view of their high absorption/encapsulation/ detection/protection properties towards small-size bioactive molecules [18]. These properties allow MOFs to adsorb small bioactive molecules within their framework and release over an extended time period with tunable release kinetics (drug delivery in disease treatment) or selective detection of important biomarkers originating from different diseases (biomarker detection in case of disease diagnosis) [19,20].

Alzheimer's disease (AD) is a neurodegenerative disease usually associated with memory loss (especially episodic memory), physical and behavioral disability, cognitive decline, and eventually, leading to death [21]. The number of people worldwide affected with AD (mostly older than 60 years) has significantly increased from 21.7 million in 1990 to 46 million in 2015, which is expected to be tripled by 2050 [22], while the complicated molecular mechanisms of AD remain unclear despite many significant studies. In addition, AD creates high economic costs and care-giving burden on humans and societies. Unfortunately, no efficient known drug is available to prevent, suppress, or reverse AD pathogenesis as almost all the efforts to produce efficient AD drugs seem to have failed [23]. Therefore, developing highly efficient diagnosis and treatment methods, such as targeted therapy for the diagnosis of early-stage asymptomatic patients, seems crucial for a better understanding of the AD's progress, thereby proceeding with the early medical treatment [24,25].

Hitherto, MOFs have been widely employed to diagnose and treat cancers, but much fewer studies on diagnosing and treating other diseases such as human immunodeficiency virus (HIV), Parkinson, inflammation, AD, and bacterial infections are available [26,27]. Even though few studies have investigated the MOFs for AD diagnosis and therapy, their valuable and reliable results encourage researches to do more works on them in future [28,29]. Qu et al. [28] prepared different porphyrin-based MOFs (PMOFs) (i.e., Al-MOF, Hf-MOF, Zr-MOF, and Ni-MOF) and used them for the inhibition of beta-amyloid (Aβ, the primary biomarker of AD) aggregation since they are superior for Cu2+ chelation and photooxidation. It was found that Hf-based MOF was the most efficient material not only for the inhibition of Aβ aggregation but also for its photooxidation. The Hf-MOF nanoparticles were modified with Aβ-targeting peptide (LPFFD) to enhance their targeting cellular Aβ and photooxidation efficiency. The results obtained from in vitro and in vivo experiments verified that modified Hf-MOFs could decrease Aβ-induced toxicity and cause greater longevity of the AD transgenic C.elegans CL2006 strain. It was also found that the synthesized PMOFs showed a wonderful Cu-chelating ability mainly due to the high affinity of carboxyl-porphyrin with Cu2+ ions.

In efforts to repress the downfall of visible light [30,31], Wang et al. [32] synthesized the near-infrared (NIR)-activated porphyrinic MOF (PCN-224) via coordinating organic TCPP (tetra-kis(4-carboxyphenyl)porphyrin) ligands with Zr4+ ions. The as-synthesized PCN-224 nanoparticles exhibited good biocompatibility, great photo‑oxygenation effectiveness, and excellent structural stability, suggesting that the activated PCN-224 nanoparticles by NIR light could effectively prevent the self-assembly of monomeric Aβ into β-sheet-rich structure, resulting in the AD prevention. Hence, it was thought that MOFs could be promising materials for diagnosing and treating AD [33,34]. Despite many recent developments of MOFs in AD diagnosis and therapy applications, no comprehensive review has yet been reported. The present review focuses on the latest applications of MOF-based materials used for diagnosing and treating AD. In this review, the utilization of MOFs for detecting AD biomarkers is critically discussed with illustrative examples of MOF-based materials for toxic metal ions detection. Recent developments of MOF materials as MRI contrast agents are also discussed to offer the challenges and future outlook in the area.