Alzheimer’s Disease: Understanding the Disease, Current Treatments, and the Promise of Nanomedicine

Alzheimer’s Disease (AD) is the leading cause of dementia, gradually breaking down memory, thinking ability, and behavior. It affects millions globally, particularly older adults. Though its exact cause is still not fully understood, scientists have identified two key changes in the brain that drive the disease: the build-up of amyloid-β (Aβ) plaques between neurons, and twisted tangles of Tau protein inside them.

Aβ plaques form when a larger protein is cut incorrectly, creating fragments that clump together into sticky deposits. These deposits block communication between brain cells and overstimulate them, leading to cell death. At the same time, Tau proteins inside neurons become defective, form tangles, and prevent the normal transport of nutrients and signals. Over time, these effects spread throughout the brain, shrinking areas like the hippocampus that are crucial for memory and learning.

Current Treatments: Easing Symptoms and Slowing Progression

Today’s approved treatments focus mostly on improving symptoms and slowing cognitive decline. Three widely prescribed drugs: Donepezil, Rivastigmine, and Galantamine, belong to a class of drugs known as acetylcholinesterase inhibitors. They work by boosting levels of acetylcholine, a chemical that helps with memory and thinking. These drugs can temporarily improve or stabilize symptoms, especially in the early to middle stages of the disease.

Memantine, another key drug, works differently. It protects brain cells from being overstimulated by glutamate, a chemical that can become toxic in excess. Memantine is sometimes used together with Donepezil or other drugs for added benefit.

Attempt at disease targeting: monoclonal antibodies

Newer treatments now target the root causes of the disease: Aβ plaques. Lab-made antibodies like Aducanumab, Lecanemab, and Donanemab help the brain’s immune system clear these harmful deposits. However, a common side effect seen with these monoclonal antibodies (mAbs) are amyloid-related imaging abnormalities (ARIA) - changes in the brain’s blood vessels caused by the immune system reacting to cleared Aβ plaques, seen during MRI scans. ARIA can lead to swelling (ARIA-E) or small brain hemorrhages (ARIA-H). Most cases are mild and don’t cause symptoms, but some can be serious, leading to headaches, confusion, or requiring the treatment to be paused or stopped. ARIA can largely be attributed to mis-targeting of mAbs in the nervous system, requiring development of more precise delivery methods.

Application of nanomedicine

To improve treatment efficacy and reduce side effects, researchers are turning to nanomedicine and the use of nanoparticles (NPs) to deliver drugs more effectively to the brain. These particles are extremely small (often 1,000 times thinner than a human hair) and can be designed to carry drugs past the blood-brain barrier (BBB), a protective layer that blocks most substances from entering the brain.

There are different types of nanoparticles being explored in Alzheimer’s research:

1. Liposomes

Liposomes are tiny fat-based bubbles that can carry both water-soluble and fat-soluble drugs. They’re biocompatible (safe for the body) and can be modified to cross the BBB. In AD, liposomes have been used to carry existing drugs like Donepezil and natural compounds like Curcumin. However, liposomes can sometimes break down quickly in the bloodstream and may not always reach the target area efficiently without further modification.

2. Chitosan Nanoparticles (ChNPs)

Made from chitosan, a natural substance derived from shellfish, these particles stick well to mucosal surfaces and are used in intranasal drug delivery. They’ve been used to deliver drugs like Rivastigmine and Piperine directly to the brain through the nose, increasing how much of the drug gets to the brain while reducing unwanted effects in the rest of the body. But, chitosan can be sensitive to environmental changes (like pH or temperature), which may affect stability and drug release.

3. PLGA Nanoparticles

PLGA (poly-lactic-co-glycolic acid) is a biodegradable material often used to make nanoparticles that release drugs slowly over time. These have been used to deliver Galantamine and Curcumin more effectively to the hippocampus, improving memory in AD models. While promising, PLGA particles sometimes face challenges in large-scale production and maintaining consistent drug release profiles.

4. Gold Nanoparticles (AuNPs)

Gold NPs are especially interesting because they can interfere directly with Aβ plaque formation. They act like “nano-chaperones,” redirecting toxic protein clumps into less harmful forms. These show positive results in lab and animal studies by reducing plaque build-up and improving memory. However, gold NPs can accumulate in brain tissue and cause inflammation, making safety a concern for long-term use.

Antibody-Loaded Nanoparticles: Smarter Targeting of Plaques

One of the more advanced strategies in nanomedicine involves loading mAbs into nanoparticles. This allows for more precise delivery to Aβ plaques while avoiding some of the side effects seen with free-floating antibodies. In experimental models, scientists have used PLGA nanoparticles coated with chitosan to help the particles stay stable and travel through the bloodstream. These particles are then linked to mAbs specifically designed to recognize Aβ plaques. Because of their size and surface design, they remain mostly within the brain’s blood vessels, targeting the plaque deposits that build up around them. This system improves how much of the antibody reaches the brain, boosts its ability to bind to Aβ, and may lower the risk of widespread inflammation. It’s a promising step toward safer, more targeted treatment. However, this is still warranting further investigation in living models before these being applied to real patients.

"Loading mAbs into nanoparticles allows for more precise delivery to Aβ plaques while avoiding some of the side effects seen with free-floating antibodies (...)"

While nanomedicine offers many advantages, it’s not without its downsides. Some types of NPs may trigger immune responses or cause brain irritation. Others may not be stable in the body, breaking down too quickly. Intranasal delivery, though promising, can be limited by enzymes in the nose that degrade drugs before they reach the brain. Manufacturing nanoparticles is also complex and expensive. Producing them at scale requires strict control over their size, surface structure, and drug-carrying ability. Regulatory approval is another challenge, as long-term safety in humans is still being evaluated.

Overall, Alzheimer’s treatments have moved from simple symptom control to more targeted and disease-modifying strategies. Medications like Donepezil, Rivastigmine, Memantine, and newer antibody therapies offer hope, but also come with limits. Nanomedicine stands out as a powerful tool for the next generation of treatments, offering more precise drug delivery, targeting underlying disease mechanisms, and making use of natural compounds that were once too difficult to deliver effectively. However, before nanomedicine can become part of standard Alzheimer’s care, its safety, cost, and production challenges must be addressed. Still, it represents a major step toward more effective, personalized, and long-lasting solutions for a disease that continues to impact millions.

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This article was written by Shriya Singh and edited by Julia Dabrowska, with graphics produced by Eve Cottenden. If you enjoyed this article, be the first to be notified about new posts by signing up to become a WiNUK member (top right of this page)! Interested in writing for WiNUK yourself? Contact us through the blog page and the editors will be in touch.