Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to worsening cognitive impairment, and the condition remains an important health problem worldwide. Due to an ageing population, the prevalence of AD is expected to increase, requiring the development of effective methods for its diagnosis and treatment. Nanotechnology, with its distinctive capacity to modify and manipulate materials at the nanoscale, has paved novel avenues in AD investigation. This article provides the latest overview of recent findings on the topic, illustrating the multidisciplinary nature of nanotechnology in countering the hurdles of AD. AD remains a formidable opponent in the neurodegenerative disease arena. Despite extensive research, there are no effective treatments for AD. Nanotechnology has entered as an impactful new front in the battle against this debilitating disease. This review article provides an overview of recent applications of nanotechnology-based tools for the progression of understanding, diagnosing, and treatment of AD. It promotes new innovative methods of prevention such as drug-delivery systems, targeting of amyloid, early detection techniques, neuroprotection, gene therapy, cerebral blood flow improvement, tau protein control and personalisation of medicine.

On the other hand, the synthesis of the beta-amyloid (Aβ) protein in AD involves the successive cleavage of a larger precursor protein called amyloid precursor protein (APP). APP is cleaved by the enzymes beta-secretase and gamma-secretase. Beta-secretase cleaves APP at position 599, yielding a fragment. This fragment is then further processed by the so-called gamma-secretase, producing differently sized Aβ peptides, including the most toxic form, Aβ 42. Aβ 42 is prone to accumulate and create insoluble plaques in the brain between neurons. These plaques prevent communication between neurons, causing neuronal damage, inflammation, and cognitive loss in patients with the disease. On the other hand, tau proteins primarily function to stabilise neuronal structure by promoting microtubule assembly. In AD, hyperphosphorylation alters tau protein function. Hyperphosphorylated tau proteins detach from microtubules and aggregate within neurons to form neurofibrillary tangles. These tangles block the passage of essential chemicals and organelles within neurons, leading to cell death and failure of signalling (Fig. 1). The accumulation of neurofibrillary tangles leads to the degradation of brain regions associated with memory and cognitive function, two distinguishing features of AD. Exploring these mechanisms is fundamental in devising targeted therapies to obstruct or diminish the build-up of these aberrant proteins, thereby potentially arresting the progress of the disease [1], [2]. Therefore, the translational potential of these nanotechnology-based solutions is discussed with a focus on AD research and therapy [3].

Transporting therapeutic drugs to the brain is one of the most challenging problems in AD therapy. Nanoparticles can provide a solution in this context, as they offer a versatile drug delivery platform, which enables targeted and controlled medication release in a way to cross the blood-brain barrier. In this section, all types of nanoparticles are discussed, and their use in the delivery of AD drugs is described. Nanoparticle-based drug delivery technologies have the potential to overcome many of the challenges associated with delivering therapeutic drugs to the brain in AD. The deposition of toxic proteins,  including Aβ and tau, in the brain is a pathological feature of AD, and crossing the blood-brain barrier (BBB) to reach these proteins represents a major challenge. Nanoparticle-based drug delivery systems for drugs or therapeutic substances can be functionalized with antibodies or ligands targeting Aβ or tau clumps. These nanoparticles are designed to cross the BBB and release their products within the brain to deliver medication in a targeted manner. This approach allows for higher specificity of treatment and less off-target effects when compared to systemic delivery, potentially minimizing systemic adverse effects [5].

Amyloid plaques are a hallmark of AD. These harmful protein clumps and their targeted-elimination nanoparticles have been developed. This has been an exciting and interesting area of AD research, with possible implications for future therapeutic approaches for AD. Plaques are one of the disease’s pathological clinical features and are linked to neurodegeneration [6]; however, the association between tau and amyloid deposition at the intercellular level at the neuropsychiatric level still needs to be explored. Their small size and adjustable properties enable nanoparticles to be tailored specifically for targeting Aβ aggregates. These nanoparticles can be decorated with high-affinity antibodies or ligands for Aβ. Thereby, specifically binding these nanoparticles to Aβ plaques can promote the clearance and removal of the neurotoxic effects of Aβ protein aggregates from the brain. In this context, nanotechnology offers unique approaches for the development of therapeutics that directly target the molecular basis of AD, potentially mitigating or preventing disease progression at the source by targeting Aβ aggregates. This approach is indicative of the progressive expansion of Alzheimer's research propelled by the intersection of nanotechnology and comprehension of neurodegenerative diseases [6], [7].

Timely diagnosis is important in the management of AD. Nanoparticle-based imaging agents, for example, in MRI and PET scans, enable the early detection of AD-associated illness. Recent advances in early detection methods are greatly influenced by the application of imaging modalities based on nanoparticles. Nanoparticles functionalized with specific ligands or antibodies [5] are used as contrast agents for imaging modalities such as MRI and PET scans. Biomarkers associated with Alzheimer’s, such as Aβ or tau. These nanoparticles have higher sensitivity and accuracy to detect slight changes related to AD at early stages. The breakthrough supports earlier diagnosis of the disease, seeking tracking before clinical symptoms appear and paves the way for early therapies, which can potentially enhance the prognosis and quality of life of patients suffering from Alzheimer’s. The combination of nanotechnology and advanced imaging techniques is the key to earlier diagnosis [8].

The establishment of nanoparticles against this dreadful neurodegenerative disorder is very few and promising, which can prevent neuronal injury as well as enhance recovery. This dual role is important because AD is marked by gradual neuronal loss and destruction. This means that when designed in the form of nanoparticles, they not only protect against neurotoxicity but they are also able to promote the growth and repair of brain cells by preparing a delivery system for neuroprotective medicines and growth factors. These nanoparticles are capable of carrying drugs to targeted sites, reducing the chances of systemic toxicity and off-target action. Although it is an emerging field, the implications of this approach are enormous, as it may not only stop the progression of AD but also restore the lost cognitive functions, giving some hope to AD-afflicted subjects for a better quality of life. The use of nanotechnology for neuroprotection and regeneration in AD demonstrates the interdisciplinary attempts of improving these therapeutic strategies rather than just the symptomatic approach to these diseases [9]. Moreover, nanotechnology is helping to advance gene therapy and treatment for the abnormal tau protein accumulation, two factors that are critical in the fight against AD. In gene therapy, nanoparticles are used as a vector for therapeutic genes that alter the expression of specific proteins linked to a disease [9]. Such an approach has the potential to regulate the production of amyloid-beta and tau proteins, the major players in AD. In tau proteinopathies, for example, nanoparticles can be optimized to selectively target and clear excessive toxic tau aggregates from the brain. They can attenuate tau-induced neurotoxicity via the delivery of therapeutic drugs or RNA interference molecules. These developments signify a transition across generations of Alzheimer's science, where nanotechnology-delivered approaches are being explored to potentially alter the course of the disease [10]. Furthermore, optimizing cerebral blood flow and oxygen delivery to brain cells is vital in AD therapeutics. Nanotechnology allows for personalized treatments, tailoring interventions to individual AD profiles. This review proposes a possible revolution that nanotechnology may bring to the domain of AD research and therapy and gives a summary of unresolved issues that need to be studied and developed in this field [11].