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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Is Open Access

      Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics


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          Currently, 47 million people live with dementia globally, and it is estimated to increase more than threefold (~131 million) by 2050. Alzheimer’s disease (AD) is one of the major causative factors to induce progressive dementia. AD is a neurodegenerative disease, and its pathogenesis has been attributed to extracellular aggregates of amyloid β (Aβ) plaques and intracellular neurofibrillary tangles made of hyperphosphorylated τ-protein in cortical and limbic areas of the human brain. It is characterized by memory loss and progressive neurocognitive dysfunction. The anomalous processing of APP by β-secretases and γ-secretases leads to production of Aβ 40 and Aβ 42 monomers, which further oligomerize and aggregate into senile plaques. The disease also intensifies through infectious agents like HIV. Additionally, during disease pathogenesis, the presence of high concentrations of Aβ peptides in central nervous system initiates microglial infiltration. Upon coming into vicinity of Aβ, microglia get activated, endocytose Aβ, and contribute toward their clearance via TREM2 surface receptors, simultaneously triggering innate immunoresponse against the aggregation. In addition to a detailed report on causative factors leading to AD, the present review also discusses the current state of the art in AD therapeutics and diagnostics, including labeling and imaging techniques employed as contrast agents for better visualization and sensing of the plaques. The review also points to an urgent need for nanotechnology as an efficient therapeutic strategy to increase the bioavailability of drugs in the central nervous system.

          Most cited references101

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          Neuroinflammation in Alzheimer's disease.

          Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.
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            Alzheimer's disease.

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              The path to personalized medicine.


                Author and article information

                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                19 July 2019
                : 14
                : 5541-5554
                [1 ]Department of Immunology and Nano-Medicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University , Miami, FL 33199, USA
                Author notes
                Correspondence: Madhavan NairDepartment of Immunology and Nano-Medicine, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University , 11200 SW 8th Street, Miami, FL33199, USATel +1 305 348 1493Email nairm@ 123456fiu.edu
                © 2019 Tiwari et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                : 05 January 2019
                : 02 March 2019
                Page count
                Figures: 7, Tables: 1, References: 103, Pages: 14

                Molecular medicine
                amyloid beta,amyloidogenesis,amyloid precursor proteins,β-secretases,γ-secretases,tau phosphorylation


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