Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of Alzheimer’s disease
Abstract Evidence suggests that increased level/aggregation of β-amyloid (Aβ) peptide, together with enhanced phosphorylation/aggregation of tau protein, play a critical role in the development of Alzheimer’s disease (AD), the leading cause of dementia in the elderly. At present, AD diagnosis is bas...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-01957-5 |
| _version_ | 1797556754641321984 |
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| author | Karthivashan Govindarajan Satyabrata Kar |
| author_facet | Karthivashan Govindarajan Satyabrata Kar |
| author_sort | Karthivashan Govindarajan |
| collection | DOAJ |
| description | Abstract Evidence suggests that increased level/aggregation of β-amyloid (Aβ) peptide, together with enhanced phosphorylation/aggregation of tau protein, play a critical role in the development of Alzheimer’s disease (AD), the leading cause of dementia in the elderly. At present, AD diagnosis is based primarily on cognitive assessment, neuroimaging, and immunological assays to detect altered levels/deposition of Aβ peptides and tau protein. While measurement of Aβ and tau in the cerebrospinal fluid/blood can indicate disease status, neuroimaging of aggregated Aβ and tau protein in the brain using positron emission tomography (PET) enable to monitor the pathological changes in AD patients. With advancements in nanomedicine, several nanoparticles, apart from drug-delivery, have been used as a diagnostic agent to identify more accurately changes in AD patients. Recently, we reported that FDA approved native PLGA nanoparticles can interact with Aβ to inhibit its aggregation/toxicity in cellular and animal models of AD. Here, we reveal that fluorescence labelled native PLGA following acute intracerebellar injection can identify majority of the immunostained Aβ as well as Congo red labelled neuritic plaques in the cortex of 5xFAD mice. Labelling of plaques by PLGA is apparent at 1 h, peak around 3 h and then start declining by 24 h after injection. No fluorescent PLGA was detected in the cerebellum of 5xFAD mice or in any brain regions of wild-type control mice following injection. These results provide the very first evidence that native PLGA nanoparticles can be used as a novel nano-theragnostic agent in the treatment as well as diagnosis of AD pathology. |
| first_indexed | 2024-03-10T17:07:24Z |
| format | Article |
| id | doaj.art-f940fc2de1a947c9a1509f251e67a5ea |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-03-10T17:07:24Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-f940fc2de1a947c9a1509f251e67a5ea2023-11-20T10:47:36ZengBMCJournal of Nanobiotechnology1477-31552023-07-0121111410.1186/s12951-023-01957-5Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of Alzheimer’s diseaseKarthivashan Govindarajan0Satyabrata Kar1Departments of Medicine (Neurology), Centre for Prions and Protein Folding Diseases, Neuroscience and Mental Health Institute, University of AlbertaDepartments of Medicine (Neurology), Centre for Prions and Protein Folding Diseases, Neuroscience and Mental Health Institute, University of AlbertaAbstract Evidence suggests that increased level/aggregation of β-amyloid (Aβ) peptide, together with enhanced phosphorylation/aggregation of tau protein, play a critical role in the development of Alzheimer’s disease (AD), the leading cause of dementia in the elderly. At present, AD diagnosis is based primarily on cognitive assessment, neuroimaging, and immunological assays to detect altered levels/deposition of Aβ peptides and tau protein. While measurement of Aβ and tau in the cerebrospinal fluid/blood can indicate disease status, neuroimaging of aggregated Aβ and tau protein in the brain using positron emission tomography (PET) enable to monitor the pathological changes in AD patients. With advancements in nanomedicine, several nanoparticles, apart from drug-delivery, have been used as a diagnostic agent to identify more accurately changes in AD patients. Recently, we reported that FDA approved native PLGA nanoparticles can interact with Aβ to inhibit its aggregation/toxicity in cellular and animal models of AD. Here, we reveal that fluorescence labelled native PLGA following acute intracerebellar injection can identify majority of the immunostained Aβ as well as Congo red labelled neuritic plaques in the cortex of 5xFAD mice. Labelling of plaques by PLGA is apparent at 1 h, peak around 3 h and then start declining by 24 h after injection. No fluorescent PLGA was detected in the cerebellum of 5xFAD mice or in any brain regions of wild-type control mice following injection. These results provide the very first evidence that native PLGA nanoparticles can be used as a novel nano-theragnostic agent in the treatment as well as diagnosis of AD pathology.https://doi.org/10.1186/s12951-023-01957-5Alzheimer’s diseaseβ-amyloidPLGA nanoparticles5xFAD miceNano-theragnostic |
| spellingShingle | Karthivashan Govindarajan Satyabrata Kar Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of Alzheimer’s disease Journal of Nanobiotechnology Alzheimer’s disease β-amyloid PLGA nanoparticles 5xFAD mice Nano-theragnostic |
| title | Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of Alzheimer’s disease |
| title_full | Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of Alzheimer’s disease |
| title_fullStr | Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of Alzheimer’s disease |
| title_full_unstemmed | Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of Alzheimer’s disease |
| title_short | Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of Alzheimer’s disease |
| title_sort | detection of β amyloid aggregates plaques in 5xfad mice by labelled native plga nanoparticles implication in the diagnosis of alzheimer s disease |
| topic | Alzheimer’s disease β-amyloid PLGA nanoparticles 5xFAD mice Nano-theragnostic |
| url | https://doi.org/10.1186/s12951-023-01957-5 |
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