1 Introduction

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that stands as the most common cause of dementia, affecting millions of individuals worldwide. Characterized by cognitive decline, memory loss, and behavioral changes, AD imposes a significant burden not only on patients but also on caregivers and healthcare systems globally. The pathophysiology of AD is complex, involving the accumulation of amyloid-beta (Aβ) plaques, the formation of neurofibrillary tangles composed of hyperphosphorylated tau protein, and widespread neuronal loss. Despite extensive research and the development of various therapeutic strategies, there remains no cure for AD, and current treatments are primarily symptomatic, providing only temporary relief without altering the disease's course (Weber-Adrian, 2019; Owens et al., 2021). The progressive nature of AD and the lack of effective disease-modifying treatments underscore the urgent need for innovative therapeutic approaches (Ghaffari et al., 2020).

Given the limitations of existing therapies, there is a growing interest in novel approaches that target the underlying molecular and genetic mechanisms of AD. Gene therapy, which involves the modification or manipulation of gene expression within a patient's cells, offers a promising avenue for the treatment of AD. Unlike conventional therapies that focus on alleviating symptoms, gene therapy aims to correct or modulate the genetic defects and pathological processes that drive the disease. This approach has the potential to not only slow the progression of AD but also to address the root causes of the disorder (Loera-Valencia et al., 2018; Sudhakar and Richardson, 2018). Advances in gene delivery systems, including viral and non-viral vectors, along with breakthroughs in gene-editing technologies like CRISPR/Cas9, have paved the way for innovative gene therapy strategies that could revolutionize the treatment of AD (Rudenko and Sholomon, 2023; Unnisa et al., 2023).

This study will provide a comprehensive analysis of the current status and future prospects of gene therapy in the treatment of Alzheimer's disease (AD). It will explore the genetic basis of AD, the mechanisms and targets of gene therapy, and the current therapeutic strategies. The study will also discuss ongoing research and clinical trials, addressing the challenges and limitations of gene therapy in this context. By synthesizing the latest research and insights, this study will offer a detailed explanation of the critical role that gene therapy plays in tackling Alzheimer's disease.

2 Genetic Underpinnings of Alzheimer's Disease

2.1 Key genetic mutations in AD

Alzheimer's disease (AD) has been extensively studied in the context of genetic predispositions, particularly with mutations in the APP (Amyloid Precursor Protein), PSEN1 (Presenilin 1), and PSEN2 (Presenilin 2) genes. These mutations are most commonly associated with early-onset familial Alzheimer's disease (EOAD), which follows an autosomal dominant inheritance pattern. APP mutations were among the first to be identified and are known to influence the production of amyloid-beta (Aβ), a peptide that aggregates to form the plaques characteristic of AD. Mutations in PSEN1 are the most common cause of EOAD, accounting for the majority of cases, and are often associated with a more aggressive disease course (Gao et al., 2019). Meanwhile, PSEN2 mutations are rarer and typically result in a later onset compared to PSEN1 mutations, although they still contribute to familial AD (Guven et al., 2021).

The APOE (Apolipoprotein E) gene, particularly the ε4 allele, plays a significant role in sporadic forms of AD, which are more common than familial cases. The presence of the APOE ε4 allele is associated with an increased risk of developing late-onset AD (LOAD) and is considered the strongest genetic risk factor for this form of the disease. Interestingly, in the context of autosomal dominant AD, the APOE ε4 allele also influences disease onset and severity, particularly in those carrying APP and PSEN1 mutations, highlighting the complex interplay between these genetic factors (Almkvist and Graff, 2021).

2.2 Pathophysiology and genetic influence

The mutations in APP, PSEN1, and PSEN2 genes primarily influence the production and processing of amyloid-beta, leading to its accumulation in the brain, a hallmark of AD. APP mutations typically increase the production of the amyloidogenic Aβ42 peptide, which is prone to aggregation. Mutations in PSEN1 and PSEN2 are known to affect the gamma-secretase complex, which plays a crucial role in the cleavage of APP to produce Aβ42. This dysregulation leads to an increased ratio of Aβ42 to Aβ40, further promoting plaque formation and neurodegeneration (Figure 1) (Costa-Laparra et al., 2023).

Genetic heterogeneity in AD has significant implications for treatment strategies. The variability in mutations, even within the same gene, can lead to differences in disease onset, progression, and response to treatment. For instance, different PSEN1 mutations can result in varying clinical phenotypes, which necessitates personalized approaches to therapy (Shim et al., 2022). Understanding these genetic differences is critical in developing targeted interventions that can more effectively address the specific pathogenic mechanisms at play in each individual.

2.3 Environmental and lifestyle interactions

In addition to genetic mutations, environmental factors and lifestyle choices play a significant role in the progression of AD, particularly in individuals with a genetic predisposition. Gene-environment interactions are crucial in modulating the onset and severity of the disease. For example, carriers of the APOE ε4 allele are more susceptible to environmental risk factors such as poor diet, lack of physical activity, and exposure to toxins, which can exacerbate the pathogenic processes leading to AD (Lacour et al., 2019).

Moreover, lifestyle interventions that target these modifiable risk factors, such as maintaining a healthy diet, regular exercise, and cognitive stimulation, have been shown to mitigate the effects of genetic risks. These findings highlight the potential for gene-environment interactions to be leveraged in preventive strategies aimed at reducing the incidence and delaying the onset of AD, particularly in genetically at-risk populations (Giau et al., 2019).

3 Mechanisms and Targets of Gene Therapy in AD

3.1 Amyloid-beta and tau pathways

Gene therapy approaches targeting the amyloid-beta (Aβ) plaques and tau tangles, the two main pathological hallmarks of Alzheimer's disease (AD), have shown promise in mitigating disease progression. The accumulation of Aβ peptides, resulting from the cleavage of amyloid precursor protein (APP) by β- and γ-secretases, triggers a cascade leading to tau hyperphosphorylation and aggregation into neurofibrillary tangles (Roda et al., 2022). Gene therapy strategies focus on either reducing the production of Aβ or enhancing its clearance. For instance, targeting the BACE1 enzyme, which is involved in Aβ production, or using gene-editing tools like CRISPR/Cas9 to correct mutations in APP, PSEN1, and PSEN2 genes, has been explored to reduce amyloid plaque formation (Figure 2) (Sun et al., 2018). Additionally, tau-targeting therapies, such as using RNA interference or CRISPR/Cas9 to prevent tau hyperphosphorylation, are being developed to reduce neurofibrillary tangle formation and subsequent neuronal damage (Kent et al., 2020).

Enhancing amyloid clearance is another critical strategy in gene therapy for AD. This can be achieved by upregulating genes involved in Aβ degradation or by modulating the immune system to enhance microglial activity, which is responsible for clearing amyloid plaques. Tau aggregation, which correlates more closely with cognitive decline than amyloid plaques, can be mitigated through gene therapies that stabilize microtubules or prevent tau from becoming hyperphosphorylated and forming tangles (Congdon and Sigurdsson, 2018).

3.2 Neuroprotective gene therapy

Neuroprotective gene therapy focuses on enhancing the expression of proteins that protect neurons from the toxic effects of Aβ and tau. One promising approach involves the delivery of genes encoding neuroprotective factors like brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF). NGF, in particular, has been shown to reduce amyloidogenesis and promote neuronal survival by interacting with the TrkA receptor, which is crucial for neuronal function (Triaca et al., 2016). Gene therapies that increase NGF expression in the brain have demonstrated the ability to reduce tau phosphorylation and prevent neurodegeneration, suggesting a potential therapeutic strategy for AD (Zhou et al., 2020).

3.3 Gene editing and CRISPR/Cas9

The advent of CRISPR/Cas9 technology has opened new avenues for gene therapy in AD by enabling precise editing of genes associated with the disease (Li and Li, 2024). CRISPR/Cas9 can be used to correct pathogenic mutations in genes such as APP, PSEN1, and PSEN2, thereby reducing the production of toxic Aβ peptides (Adji et al., 2022). Furthermore, CRISPR/Cas9 can be employed to modulate gene expression or to insert genes that confer neuroprotection, making it a versatile tool for addressing the complex genetic factors involved in AD (Lu et al., 2021).

However, the application of CRISPR/Cas9 in AD also raises significant ethical considerations and technical challenges. The potential for off-target effects, where unintended sections of DNA are edited, poses risks that need to be carefully managed. Moreover, the long-term implications of gene editing, particularly in the brain, are not fully understood, and there are concerns about the heritability of genetic modifications and their impact on future generations (Barman et al., 2020). These challenges underscore the need for thorough preclinical testing and stringent regulatory oversight to ensure the safety and efficacy of CRISPR/Cas9-based therapies for AD.

Gene therapy targeting the amyloid-beta and tau pathways, enhancing neuroprotective proteins, and utilizing CRISPR/Cas9 technology holds great promise for the treatment of Alzheimer's disease. As research progresses, these strategies may offer new hope in combating the devastating effects of AD, though careful consideration of the associated risks and ethical issues remains paramount.

4 Current Strategies in Gene Therapy for Alzheimer’s Disease

4.1 Viral vector-based therapies

Viral vectors have been at the forefront of gene therapy due to their high efficiency in delivering genetic material into target cells. Among these, adeno-associated virus (AAV) and lentivirus are particularly prominent in the context of Alzheimer’s disease (AD) research. AAV vectors are favored for their ability to infect both dividing and non-dividing cells, making them suitable for targeting neurons, which are largely non-dividing. AAV vectors are also known for their low immunogenicity and long-term expression of therapeutic genes (Ralph et al., 2006; Honig, 2018). Lentiviral vectors, on the other hand, have the capacity to integrate into the host genome, leading to stable and long-term expression of the therapeutic gene. This feature is particularly useful for chronic conditions like AD, where sustained gene expression is critical (Kumar and Woon-Khiong, 2011).

Despite the advantages, viral vectors face significant challenges in gene therapy for AD. One major challenge is the blood-brain barrier (BBB), which limits the efficient delivery of these vectors to the central nervous system (CNS). Strategies to overcome this include the development of vectors that can cross the BBB or the use of invasive methods like intracranial injections (Butt et al., 2022). Additionally, there are concerns regarding the potential for insertional mutagenesis with lentiviral vectors, where the integration of the viral genome into the host DNA could disrupt important genes and lead to oncogenesis. Advances in vector design, such as the use of integration-deficient lentiviral vectors, are being explored to mitigate these risks (Kumar and Woon-Khiong, 2011).

4.2 Non-viral gene delivery systems

Non-viral gene delivery systems, such as nanoparticles and liposomes, have gained traction due to their safety profile and flexibility. Nanoparticles can be engineered to bypass the BBB and deliver genes directly to the brain, reducing systemic toxicity and improving the specificity of gene delivery (Arora et al., 2021). Liposomes, which are lipid-based carriers, can encapsulate nucleic acids and protect them from degradation, allowing for efficient delivery to target cells. Both nanoparticles and liposomes can be modified with targeting ligands to enhance their delivery to specific cell types, including neurons affected by AD.

Recent advances in nanotechnology have led to the development of multifunctional nanoparticles that not only deliver genes but also facilitate their controlled release in the brain. These nanoparticles can be designed to respond to specific stimuli, such as pH or temperature changes, which are characteristic of diseased tissues, ensuring that the therapeutic genes are released only where they are needed (Ediriweera et al., 2021). Furthermore, nanotechnology allows for the co-delivery of multiple therapeutic agents, such as genes and drugs, which could provide a more comprehensive approach to treating AD by targeting multiple pathways simultaneously (Annu et al., 2022).

4.3 Gene therapy with stem cells

Gene therapy combined with stem cell technology offers a promising strategy for neuroregeneration in AD. Induced pluripotent stem cells (iPSCs) can be genetically modified to overexpress neuroprotective genes and then transplanted into the brain to replace lost or damaged neurons. These gene-modified stem cells not only integrate into the existing neural network but also provide a continuous source of therapeutic proteins that can mitigate the progression of AD (Haridhasapavalan et al., 2019).

The use of iPSCs, which are derived from a patient’s own cells, circumvents the ethical and immunological issues associated with embryonic stem cells. By using gene-editing tools like CRISPR/Cas9, iPSCs can be corrected for any genetic mutations before being differentiated into neurons and transplanted back into the patient’s brain. This approach not only aims to replace lost neurons but also to correct the underlying genetic causes of AD, offering a potentially curative treatment (Komatsu et al., 2019). However, the clinical translation of these therapies requires further research to ensure the safety and efficacy of the genetically modified cells, particularly in terms of their long-term integration and function in the brain.

5 Current Research and Clinical Trials

5.1 Preclinical studies

Preclinical studies in animal models of Alzheimer's disease (AD) have provided valuable insights into the potential efficacy of gene therapy. These models, primarily transgenic mice that express human genes associated with familial AD, have been instrumental in evaluating the effects of gene therapy interventions. For instance, the use of adeno-associated virus (AAV) vectors to deliver neuroprotective genes such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) has shown promise in reducing amyloid-beta plaque formation and enhancing neuronal survival (Tuszynski et al., 2015). Similarly, gene therapy approaches targeting the tau protein have demonstrated efficacy in reducing tau pathology and improving cognitive function in these models (Tedeschi et al., 2021). These successes highlight the potential of gene therapy as a treatment for AD.

Despite the promising results in animal models, translating these findings to human clinical trials has been fraught with challenges. One major issue is the difference in disease pathology between animals and humans, which can result in therapies that are effective in animal models failing to show similar efficacy in humans. For example, the complexity of the human brain and the multifactorial nature of AD mean that therapies targeting a single pathway may not be sufficient to halt disease progression (Banik et al., 2015). Additionally, the blood-brain barrier (BBB) poses a significant hurdle in delivering gene therapies effectively to the human brain, a challenge that is less pronounced in animal models (LaFerla and Green, 2012).

5.2 Completed and ongoing clinical trials

Several clinical trials have been initiated to test the safety and efficacy of gene therapies in AD patients. Notably, early trials focused on the delivery of NGF to the brain using AAV vectors. Although these trials demonstrated the safety of the approach, the results were inconclusive regarding cognitive benefits, partly due to challenges in achieving adequate vector delivery and gene expression in target areas (Castle et al., 2020). More recent trials are exploring the use of advanced delivery methods, including convection-enhanced delivery and MRI-guided stereotactic surgery, to improve the accuracy and efficacy of gene delivery (Tuszynski et al., 2015).

The outcomes of these clinical trials have highlighted several challenges in the application of gene therapy for AD. One of the primary challenges has been the limited spread of the therapeutic gene within the brain, resulting in suboptimal engagement of target neurons. Furthermore, the heterogeneity of AD, both in terms of genetic mutations and disease progression, complicates the design of clinical trials and the interpretation of results (Yiannopoulou et al., 2019). Despite these challenges, ongoing trials continue to refine gene delivery techniques and explore combination therapies to enhance therapeutic outcomes.

5.3 Emerging research trends

To address the challenges observed in earlier trials, researchers are investigating new viral vectors and delivery methods that can achieve more widespread and targeted gene expression in the brain. For example, the development of modified AAV vectors with enhanced tropism for neurons and the use of non-viral delivery systems such as nanoparticles are promising approaches under investigation (Chen et al., 2020). Additionally, advances in real-time imaging techniques, such as MRI-guided delivery, are being incorporated into clinical trial designs to improve the precision of gene therapy administration.

Emerging research is also focusing on identifying novel therapeutic targets for gene therapy in AD. Beyond amyloid-beta and tau, researchers are exploring the potential of targeting neuroinflammation, synaptic dysfunction, and oxidative stress, all of which play critical roles in AD pathogenesis (Owens et al., 2021). These efforts are aimed at developing multifaceted gene therapy approaches that can address the various aspects of AD pathology, offering a more comprehensive treatment strategy.

6 Challenges and Limitations of Gene Therapy in AD

6.1 Technical and biological barriers

One of the most significant technical challenges in applying gene therapy for Alzheimer's disease (AD) is the blood-brain barrier (BBB). The BBB is a selective barrier that protects the brain from potentially harmful substances in the bloodstream but also significantly limits the ability of therapeutic agents, including viral and non-viral vectors, to reach the brain in adequate concentrations. Strategies to overcome this include using modified viral vectors like adeno-associated viruses (AAVs) that can cross the BBB more effectively, and employing non-viral delivery systems such as nanoparticles that are designed to bypass or transiently disrupt the BBB (Weber-Adrian, 2019). However, ensuring that these therapies reach specific regions of the brain affected by AD while minimizing off-target effects remains a formidable challenge (Arora et al., 2021).

Another major concern is the long-term safety and efficacy of gene therapy. Ensuring sustained expression of the therapeutic gene over time without triggering an immune response or causing toxicity is critical. The risk of insertional mutagenesis, where the integration of the therapeutic gene disrupts essential host genes, remains a significant safety concern, particularly with viral vectors that integrate into the host genome, like lentiviruses (Chen et al., 2020). Non-integrating vectors or episomal vectors may offer a safer alternative, but they often suffer from reduced expression over time, requiring repeated administration, which may not be feasible or desirable in a chronic condition like AD (Tedeschi et al., 2021).

6.2 Ethical considerations

The application of gene editing technologies, particularly CRISPR/Cas9, in treating AD raises significant ethical concerns. The possibility of off-target effects and the long-term implications of gene edits, especially if they are heritable, necessitate rigorous ethical scrutiny. Moreover, the need for long-term monitoring of patients who receive gene therapy to track the persistence and effects of the therapy, including any unintended consequences, adds another layer of complexity. The potential for unforeseen side effects that may only become apparent years after treatment highlights the ethical obligation to ensure thorough and long-term follow-up.

Public perception of gene therapy is influenced by concerns over safety, ethics, and the potential for misuse, such as in germline editing. This, combined with the complex regulatory landscape that governs the approval of gene therapies, presents significant hurdles. Regulatory bodies require extensive evidence of safety and efficacy, which can delay the availability of these therapies to patients who need them. Moreover, the ethical issues surrounding consent, especially in patients with cognitive impairment, pose challenges in the context of clinical trials and treatment implementation (Davis, 2017).

6.3 Clinical efficacy and cost

Gene therapy is one of the most expensive forms of treatment due to the complex processes involved in vector production, delivery, and patient monitoring. This high cost poses a significant barrier to widespread adoption, especially when the clinical outcomes are still under investigation. Balancing the enormous costs associated with gene therapy against the potential, but as yet unproven, benefits is a significant challenge for healthcare systems. The cost-effectiveness of gene therapy in AD will need to be thoroughly evaluated, considering the long-term benefits and the reduction in care costs that successful treatment could bring (Shellhaas et al., 2021).

Another significant challenge is demonstrating the long-term efficacy of gene therapy across diverse patient populations. The heterogeneity of AD, with its varying genetic, environmental, and lifestyle factors, makes it difficult to predict how different individuals will respond to the same gene therapy. Clinical trials need to account for this variability, but doing so increases the complexity and cost of the trials. Moreover, long-term studies are required to assess the sustained benefits of gene therapy, which can be logistically and financially challenging (Yiannopoulou et al., 2019).

While gene therapy holds great promise for treating Alzheimer's disease, it faces significant technical, ethical, and economic challenges that must be addressed. Overcoming these barriers will be crucial for realizing the full potential of gene therapy in providing long-term, effective treatments for AD.

7 Future Directions and Emerging Trends

7.1 Advancements in gene editing technologies

The CRISPR/Cas9 gene-editing technology has emerged as a powerful tool for precisely targeting and modifying specific genetic sequences associated with Alzheimer's disease (AD). Its potential applications in AD therapy are vast, ranging from correcting pathogenic mutations in genes such as APP, PSEN1, and APOE to modulating gene expression to prevent the formation of amyloid-beta plaques and neurofibrillary tangles. Recent studies have demonstrated the ability of CRISPR/Cas9 to reduce amyloid-beta production and improve cognitive function in AD mouse models, paving the way for potential human applications (Rohn et al., 2018). However, the clinical translation of CRISPR/Cas9 remains challenging due to concerns about off-target effects and the need for safe and effective delivery systems to the brain (Bhardwaj et al., 2021).

Advances in nanotechnology are contributing to the development of next-generation gene delivery systems that can overcome the limitations of current CRISPR/Cas9 applications in AD. Nanoparticles and other non-viral vectors are being explored as alternatives to traditional viral vectors, offering the potential for safer and more precise delivery of gene-editing tools. These systems can be engineered to cross the blood-brain barrier and deliver CRISPR/Cas9 components directly to the affected regions of the brain, minimizing systemic exposure and reducing the risk of off-target effects (Hanafy et al., 2020).

7.2 Personalized gene therapy

Personalized medicine is an emerging trend in gene therapy, particularly in the treatment of complex diseases like AD. By tailoring gene therapy approaches to an individual’s genetic profile, it is possible to achieve more effective and targeted treatments (Zhang, 2024). For instance, individuals with specific mutations in the APP or PSEN1 genes might benefit from therapies designed to correct these mutations using CRISPR/Cas9, while others with different genetic risk factors may require alternative approaches. This level of personalization holds the promise of optimizing therapeutic outcomes and minimizing adverse effects (Paquet et al., 2016; Adji et al., 2022).

Another promising direction is the combination of gene therapy with other therapeutic modalities, such as immunotherapy, pharmacotherapy, or lifestyle interventions. Combining CRISPR/Cas9-based gene editing with drugs that target amyloid-beta or tau pathways, for example, could provide a more comprehensive approach to treating AD. Additionally, gene therapy might be used to enhance the efficacy of traditional treatments, such as by increasing the expression of drug targets or by protecting neurons from the toxic effects of amyloid-beta and tau (Barman et al., 2020; Lu et al., 2021).

7.3 Exploration of new therapeutic targets

While amyloid-beta and tau have been the primary targets of AD research, emerging evidence suggests that other pathways, such as neuroinflammation and neuroprotection, may also play critical roles in the disease. Gene therapies that target these pathways could provide new avenues for treatment. For example, modulating the expression of genes involved in neuroinflammatory responses or enhancing the production of neuroprotective factors like BDNF could help slow the progression of AD and protect against neuronal loss (Hanafy et al., 2020; Lu et al., 2021).

The interplay between genetics, environment, and lifestyle is increasingly recognized as a key factor in the development and progression of AD. Future gene therapy research may focus on understanding how environmental factors such as diet, exercise, and exposure to toxins interact with genetic predispositions to influence disease risk. This knowledge could lead to the development of gene therapies that are not only tailored to an individual’s genetic profile but also take into account their environmental exposures and lifestyle choices, offering a more holistic approach to AD prevention and treatment (Adji et al., 2022).

The future of gene therapy for Alzheimer's disease lies in the continued advancement of gene-editing technologies, the development of personalized approaches, and the exploration of new therapeutic targets. These emerging trends hold the promise of transforming the treatment landscape for AD, offering hope for more effective and enduring interventions.

8 Concluding Remarks

Gene therapy represents a transformative approach in the treatment of Alzheimer's disease (AD), offering the potential to address the underlying genetic and molecular causes of this complex neurodegenerative disorder. By directly targeting pathogenic genes, such as APP, PSEN1, and APOE, gene therapy can potentially halt or even reverse the progression of AD, rather than merely alleviating symptoms. Techniques like CRISPR/Cas9 have shown promise in preclinical models, where they have successfully reduced amyloid-beta production and improved cognitive functions. Additionally, the development of advanced delivery systems, including viral vectors and nanotechnology-based approaches, has enhanced the precision and efficacy of gene therapies in reaching target brain regions while minimizing off-target effects.

Despite the promising developments, several challenges remain that must be addressed through future research. First, improving the safety and efficiency of gene delivery systems is crucial, particularly in overcoming the blood-brain barrier and achieving sustained gene expression without adverse effects. Additionally, the potential for off-target effects with gene-editing technologies like CRISPR/Cas9 must be minimized through advancements in vector design and targeting accuracy. Research should also focus on identifying new therapeutic targets beyond amyloid-beta and tau, including pathways related to neuroinflammation, oxidative stress, and synaptic dysfunction, which could offer broader treatment options for AD. Moreover, personalized gene therapy approaches that consider individual genetic profiles, environmental factors, and lifestyle choices could enhance the efficacy and safety of these treatments, providing tailored interventions for patients.

Translating the advances in gene therapy for AD from the laboratory to the clinic involves significant hurdles. Regulatory challenges, ethical considerations, and the high costs associated with gene therapy development are substantial barriers to widespread clinical adoption. Long-term studies are required to evaluate the efficacy, safety, and durability of gene therapies in diverse patient populations. Additionally, the integration of gene therapy with other treatment modalities, such as pharmacotherapy and lifestyle interventions, will be critical in achieving comprehensive and effective care for AD patients. Collaboration between researchers, clinicians, regulatory bodies, and industry partners will be essential to overcome these obstacles and ensure that gene therapy becomes a viable and accessible option for those affected by AD.

In conclusion, while significant challenges remain, the prospects of gene therapy in Alzheimer's disease are promising, offering the potential to fundamentally change the treatment landscape for this devastating condition. Continued research, innovation, and collaboration will be key to realizing the full potential of gene therapy in AD, ultimately leading to more effective and personalized treatments for patients.

Acknowledgments

The authors express gratitude to the two anonymous peer reviewers for their feedback.

Conflict of Interest Disclosure

The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

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