Abstract

Drug formulations and suitable methods for their detection play a very crucial role in the development of therapeutics towards degenerative neurological diseases. For diseases such as Alzheimer’s disease, magnetic resonance imaging (MRI) is a non-invasive clinical technique suitable for early diagnosis. In this review, we will discuss the different experimental conditions which can push MRI as the technique of choice and the gold standard for early diagnosis of Alzheimer’s disease. Here, we describe and compare various techniques for administration of nanoparticles targeted to the brain and suitable formulations of nanoparticles for use as magnetically active therapeutic probes in drug delivery targeting the brain. We explore different physiological pathways involved in the transport of such nanoparticles for successful entry in the brain. In our lab, we have used different formulations of iron oxide nanoparticles (IONPs) and protein nanocages as contrast agents in anatomical MRI of an Alzheimer’s disease (AD) brain. We compare these coatings and their benefits to provide the best contrast in addition to biocompatibility properties to be used as sustainable drug-release systems. In the later sections, the contrast enhancement techniques in MRI studies are discussed. Examples of contrast-enhanced imaging using advanced pulse sequences are discussed with the main focus on important studies in the field of neurological diseases. In addition, T1 contrast agents such as gadolinium chelates are compared with the T2 contrast agents mainly made of superparamagnetic inorganic metal nanoparticles.

Highlights

  • Alzheimer’s disease (AD) is the most common form of dementia, comprising 70–80% of the total cases

  • We have used different formulations of iron oxide nanoparticles (IONPs) and protein nanocages as contrast agents in anatomical magnetic resonance imaging (MRI) of an Alzheimer’s disease (AD) brain

  • The diagnostic modalities for brain imaging include positron electron tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI). These techniques are used in conjunction with neuropsychological testing after the appearance of first clinical symptoms to estimate the progression of the disease

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Summary

Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia, comprising 70–80% of the total cases. The key pathological events in the disease progression, such as Amyloid-β (Aβ) aggregation and phosphorylation of tau protein, can begin decades before the appearance of the first clinical symptoms Such findings have rightfully shifted the focus towards early diagnosis of these hallmarks or biomarkers [2]. The diagnostic modalities for brain imaging include positron electron tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI) These techniques are used in conjunction with neuropsychological testing after the appearance of first clinical symptoms to estimate the progression of the disease. The key to developing therapeutics for AD is the early detection of possible pathological changes, long before the onset of cognitive decline For such elusive anatomical differences, the inherent tissue contrast is not enough. One critical consideration for the development of such molecules is their ability to enter the target brain regions

Diagnostic Tracers for Targeting Brain Tissue in Alzheimer’s Disease
Modes of Brain Targeting for Detection of Alzheimer’s Disease
Across the Blood-Brain Barrier
Bypassing the Blood-Brain Barrier
Magnetic Resonance Imaging in Alzheimer’s Disease
Iron Oxide Nanoparticles as Magnetic Resonance Imaging Probes
Magnetic Resonance Imaging Probes for Alzheimer’s Disease Therapeutics
The Future Outlook for Alzheimer’s Disease Tracers

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