Multimodal Nanoprobes to Target Cerebrovascular Amyloid in Alzheimer’s Disease Brain
Open accessAbstract
Cerebral amyloid angiopathy (CAA) results from the accumulation of Aβ proteins primarily within the media and adventitia of small arteries and capillaries of the cortex and leptomeninges. CAA affects a majority of Alzheimer's disease (AD) patients and is associated with a rapid decline in cognitive reserve. Unfortunately, there is no pre-mortem diagnosis available for CAA. Furthermore, treatment options are few and relatively ineffective. To combat this issue, we have designed nanovehicles (nanoparticles-IgG4.1) capable of targeting cerebrovascular amyloid (CVA) and serving as early diagnostic and therapeutic agents. These nanovehicles were loaded with Gadolinium (Gd) based (Magnevist(®)) magnetic resonance imaging contrast agents or single photon emission computed tomography (SPECT) agents, such as (125)I. In addition, the nanovehicles carry either anti-inflammatory and anti-amyloidogenic agents such as curcumin or immunosuppressants such as dexamethasone, which were previously shown to reduce cerebrovascular inflammation. Owing to the anti-amyloid antibody (IgG4.1) grafted on the surface, the nanovehicles are capable of specifically targeting CVA deposits. The nanovehicles effectively marginate from the blood flow to the vascular wall as determined by using quartz crystal microbalance with dissipation monitoring (QCM-D) technology. They demonstrate excellent distribution to the brain vasculature and target CVA, thus providing MRI and SPECT contrast specific to the CVA in the brain. In addition, they also display the potential to carry therapeutic agents to reduce cerebrovascular inflammation associated with CAA, which is believed to trigger hemorrhage in CAA patients.
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The most common targeting approach is conjugation of Nps with antibodies or their fragments specific to various forms of Aβ.
“The most common approach is the conjugation of Nps with antibodies or their fragments specific to various forms of Aβ [63,70,71,81].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [71]
Materials and methods (§2.4) describes covalently conjugating the anti-Aβ antibody IgG4.1 to nanoparticles, and Results (§3.1) reports increased binding to DutchAβ40. The paper supports this as an example of antibody-based targeting, but does not establish that it is the most common approach or document the broader claim about antibody fragments targeting various forms of Aβ. Page numbers were not available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredOxidative stress and neuroinflammation rank as key secondary targets (10 studies), with Nps incorporating antioxidants or immunosuppressants.
“Oxidative stress and neuroinflammation rank as key secondary targets (10 studies), with Nps incorporating antioxidants (CeNCs, tannic acid, curcumin, quercetin) or immunosuppressants (dexamethasone, cyclophosphamide) to prevent neuronal death and attenuate inflammation [58,70,71,78].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [71]
The Results (section 3.1; page unavailable) report nanovehicles encapsulating curcumin and dexamethasone. The Discussion (section 4; page unavailable) describes curcumin’s antioxidant and anti-inflammatory properties and proposes reducing inflammation through targeted delivery. This paper does not establish the count of 10 studies or address the other listed compounds or prevention of neuronal death. (LLM, conf=0.86)
Experimental — accuracy not yet measuredMany theranostic systems represent parallel function combinations within single particles, where diagnostics and therapy operate independently.
“Many represent parallel function combinations within single particles, where diagnostics and therapy operate independently [70,71,74].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [71]
The Conclusions describe nanovehicles that provide MRI and SPECT contrast and can carry therapeutic agents, supporting their use as single-particle combinations of diagnostic and potential therapeutic functions. The paper does not establish that diagnostics and therapy operate independently or that this arrangement characterizes many theranostic systems; therapeutic benefit was not demonstrated. (LLM, conf=0.82)
Experimental — accuracy not yet measuredA number of studies employ multimodal approaches, combining MRI with PET, SPECT, or fluorescence imaging, which compensates for the limitations of each method individually.
“A number of studies employ multimodal approaches, combining MRI with PET [64], SPECT [70,71], or fluorescence imaging [72,75], which compensates for the limitations of each method individually.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [71]
A significant portion of studies use MRI with contrast agents based on gadolinium, SPIONs, or manganese ions, reflecting the researchers' desire to create platforms potentially applicable in clinical practice.
“A significant portion of the studies use MRI with contrast agents based on gadolinium [70,71], SPIONs [58,63,73,83], or manganese ions [72], reflecting the researchers’ desire to create platforms potentially applicable in clinical practice.”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [71]
Many studies include an antioxidant component aimed at reducing ROS and an anti-inflammatory effect via delivery of immunosuppressants.
“Many studies also include an antioxidant component aimed at reducing the level of ROS [64,72,78,80,83], and an anti-inflammatory effect, implemented through the delivery of immunosuppressants [70,71].”
From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [71]
Anti-amyloid antibody-conjugated curcumin/dexamethasone loaded gadolinium/magnetic nanoparticles enable early diagnosis, effective targeting, and therapeutic action against cerebrovascular amyloid.
“Early diagnosis, effective targeting, and as a therapeutic agent(s) of cerebrovascular amyloid”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Jaruszewski et al., 2014
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- Authors
- Jaruszewski, K. M., Curran, G. L., Swaminathan, S. K., Rosenberg, J. T., Grant, S. C., Ramakrishnan, S., Lowe, V. J., Poduslo, J. F., & Kandimalla, K. K.
- Affiliations
- Mayo Clinic (US)
- University of Minnesota (US)
- Florida State University (US)
- Corresponding author
- Kandimalla, Karunya K.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 35
- Issue
- 6
- Pages
- 1967-1976
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3970424
- OpenAlex
- W2083953683
- Cited by
- 64
- References
- 26
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 9 · 2022: 3 · 2021: 6 · 2020: 13 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 3
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Research Resources (G12RR003020)
- National Institute on Minority Health and Health Disparities (P20MD006738, G12MD007582)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- cerebral amyloid angiopathy, Alzheimer's disease, cerebrovascular amyloid, gadolinium-based contrast agents, SPECT imaging agents, curcumin, dexamethasone, anti-inflammatory therapy, cerebrovascular inflammation, hemorrhagic stroke, targeted drug delivery
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cell Line, Humans, Magnetic Resonance Imaging, Tomography, Emission-Computed, Single-Photon, Cerebral Amyloid Angiopathy, Chitosan, Mice, Plaque, Amyloid
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