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Review
. 2023 Nov 21;12(23):2669.
doi: 10.3390/cells12232669.

The Major Hypotheses of Alzheimer's Disease: Related Nanotechnology-Based Approaches for Its Diagnosis and Treatment

César Cáceres  1 , Bernardita Heusser  1 , Alexandra Garnham  1 , Ewa Moczko  1
Affiliations
Review

The Major Hypotheses of Alzheimer's Disease: Related Nanotechnology-Based Approaches for Its Diagnosis and Treatment

César Cáceres et al. Cells. .

Abstract

Alzheimer's disease (AD) is a well-known chronic neurodegenerative disorder that leads to the progressive death of brain cells, resulting in memory loss and the loss of other critical body functions. In March 2019, one of the major pharmaceutical companies and its partners announced that currently, there is no drug to cure AD, and all clinical trials of the new ones have been cancelled, leaving many people without hope. However, despite the clear message and startling reality, the research continued. Finally, in the last two years, the Food and Drug Administration (FDA) approved the first-ever medications to treat Alzheimer's, aducanumab and lecanemab. Despite researchers' support of this decision, there are serious concerns about their effectiveness and safety. The validation of aducanumab by the Centers for Medicare and Medicaid Services is still pending, and lecanemab was authorized without considering data from the phase III trials. Furthermore, numerous reports suggest that patients have died when undergoing extended treatment. While there is evidence that aducanumab and lecanemab may provide some relief to those suffering from AD, their impact remains a topic of ongoing research and debate within the medical community. The fact is that even though there are considerable efforts regarding pharmacological treatment, no definitive cure for AD has been found yet. Nevertheless, it is strongly believed that modern nanotechnology holds promising solutions and effective clinical strategies for the development of diagnostic tools and treatments for AD. This review summarizes the major hallmarks of AD, its etiological mechanisms, and challenges. It explores existing diagnostic and therapeutic methods and the potential of nanotechnology-based approaches for recognizing and monitoring patients at risk of irreversible neuronal degeneration. Overall, it provides a broad overview for those interested in the evolving areas of clinical neuroscience, AD, and related nanotechnology. With further research and development, nanotechnology-based approaches may offer new solutions and hope for millions of people affected by this devastating disease.

Keywords: Alzheimer’s disease; biomarkers; drug delivery; nanoparticles; nanotechnology; neurodegeneration; neuroscience.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Different hypotheses of Alzheimer’s disease.
Figure 2
Figure 2
Schematic illustration of the concept of Aβ cytotoxic actions in neurons. The cleavage of APP protein and Aβ generation (on the left); Aβ aggregation (on the top); the creation of the calcium channels, release of ATP, and P2X receptor activation (on the right).
Figure 3
Figure 3
Pathophysiology of tau in Alzheimer’s disease. A healthy neuron and axonal microtubule stabilized by tau, which maintains the shape of axon (on the left). A neuron with tau aggregation, neurofibrillary tangles, and microtubule depolymerization (on the right).
Figure 4
Figure 4
Potential causes and consequences of mitochondrial dysfunction, contributing to the development and progression of neurodegeneration.
Figure 5
Figure 5
Neurotransmission of the cholinergic synapse. In the synaptic cleft of a cholinergic neuron, acetylcholine (ACh) is decomposed into choline and acetic acid by acetylcholinesterase (AChE).
Figure 6
Figure 6
Microglia-mediated neuroinflammation in Alzheimer’s disease (AD). Under the pathology of AD, the accumulation of Aβ peptides and tau NFT induce microglial-like activation, which produces inflammatory cytokines, releases ROS, and causes neuronal cell death.
See this image and copyright information in PMC

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