Genetic Testing Role in Evolution of Precision Medicine

Guoli Yang^*
*Correspondence: Guoli Yang, Department of Medicine, Zhejiang University School of Medicine, Zhejiang, China, Email:

Keywords

Genetic testing • Alzheimer's disease • Neurodegenerative disorder • Psychological impact

Introduction

While age remains the most significant risk factor, genetic testing has unveiled specific genetic variants associated with Alzheimer's disease. The study of Alzheimer's disease genetics began in the early 1990s when researchers identified mutations in the amyloid precursor protein and presenilin genes as causative factors in familial Alzheimer's disease. These rare, highly penetrant mutations were found in families with a strong history of the disease and typically led to early-onset Alzheimer's disease. Further genetic studies revealed that the apolipoprotein gene is a major genetic risk factor for lateonset Alzheimer's disease which is the most common form of the disease. The ε4 allele is associated with an increased risk of developing LOAD, while allele appears to be protective. Over the past few decades, the field of genetic testing for Alzheimer's disease has undergone significant evolution. The identification of FAD-associated mutations in the 1990s marked the beginning of genetic testing for Alzheimer's disease. Testing primarily focused on families with a strong history of the disease. The discovery of the APOE allele's association with LOAD prompted genetic testing for this risk factor. APOE genotyping became widely available, allowing individuals to determine their genetic risk. With the advent of next-generation sequencing technologies, genetic testing for Alzheimer's disease expanded to include comprehensive sequencing of genes associated with the disease. PRS has become a valuable tool in predicting an individual's susceptibility to the disease. Large-scale GWAS have identified numerous genetic variants associated with Alzheimer's disease, shedding light on novel risk factors and potential therapeutic targets [1].

Literature Review

Genetic testing helps estimate an individual's risk of developing Alzheimer's disease. This information can inform preventive measures and early screening recommendations. Genetic testing is essential for enrolling participants in clinical trials targeting specific genetic variants associated with Alzheimer's disease. Genetic data collected from individuals with Alzheimer's disease contribute to ongoing research efforts, advancing our understanding of disease mechanisms and potential therapies. Genetic testing provides an opportunity for genetic counseling, allowing individuals and families to make informed decisions about family planning and care planning. Learning about one's genetic risk for Alzheimer's disease can have significant psychosocial implications, leading to anxiety, depression and existential distress. Protecting the privacy of genetic data and ensuring informed consent are critical ethical considerations in genetic testing. Genetic information can lead to stigmatization and discrimination, both in healthcare settings and in insurance and employment contexts. Knowing one's genetic risk may lead to a psychological burden, potentially affecting mental health and quality of life. Variants of uncertain significance and polygenic risk scores present challenges in interpreting genetic test results and their clinical significance. Genetic testing can identify individuals at higher risk, allowing for early intervention, lifestyle modifications, and targeted preventive measures. As our understanding of genetic factors influencing Alzheimer's disease grows, precision medicine approaches can target specific genetic vulnerabilities, potentially leading to more effective treatments [2].

Discussion

By identifying high-risk individuals, genetic testing contributes to population health strategies for Alzheimer's disease prevention and management. Ongoing research aims to identify and validate biomarkers for Alzheimer's disease, allowing for earlier and more accurate diagnosis. Genetic discoveries continue to unveil potential therapeutic targets, paving the way for innovative treatments and disease-modifying interventions. Clinical trials targeting specific genetic variants will become increasingly common, offering hope for more personalized and effective therapies. Ethical guidelines and frameworks will evolve to address the unique challenges posed by genetic testing in Alzheimer's disease. Advances in data analytics and artificial intelligence will enhance our ability to interpret complex genetic data and identify novel associations. The evolution of genetic testing in Alzheimer's disease has transformed our approach to understanding, diagnosing, and potentially treating this devastating condition. From the early identification of FAD-associated mutations to the emergence of polygenic risk scores, genetic testing has become an integral component of precision medicine for Alzheimer's disease patients. While challenges related to psychosocial impact, privacy, and interpretation persist, the promise of early intervention, personalized treatment, and innovative therapies underscores the importance of genetic testing in Alzheimer's disease care. As research continues to uncover genetic insights into this complex disease, the future holds hope for more effective treatments and prevention strategies, offering relief to individuals and families affected by Alzheimer's disease [3].

Alzheimer's disease is a complex neurodegenerative condition that affects millions of individuals worldwide. With an aging global population, the prevalence of AD is expected to rise significantly in the coming decades. While there is currently no cure for AD, advances in genetic testing have played a pivotal role in the development of precision medicine approaches for the care and management of AD patients. The understanding of genetic factors in Alzheimer's disease has evolved over time, with significant milestones. Early observations noted that AD often ran in families, suggesting a genetic component to the disease. However, these cases represented a small fraction of AD diagnoses. The discovery of the APOE gene in the early 1990s marked a significant breakthrough. Variants of this gene, particularly APOE ε4, were found to be strong risk factors for late-onset AD, the most common form of the disease. Large-scale GWAS have identified numerous genetic variants associated with late-onset AD. These studies have shed light on various biological pathways implicated in the disease, including those related to amyloid beta and tau proteins. Beyond APOE, rare genetic variants with moderate to high penetrance have been identified in genes like TREM2 and SORL1, offering valuable insights into AD risk and pathogenesis. PRS, calculated based on the cumulative effect of multiple genetic variants, have been developed to estimate an individual's genetic risk for AD. PRS can help identify individuals at higher risk and guide early interventions [4].

In cases with atypical or early-onset symptoms, genetic testing can confirm a diagnosis of familial Alzheimer's disease caused by specific mutations. Genetic testing helps identify eligible participants for clinical trials targeting specific genetic variants, accelerating drug development efforts. Genetic data can be used to monitor disease progression and treatment response, enabling adjustments in care plans. In this article, we will explore the evolution of genetic testing in supporting precision medicine for Alzheimer's disease patients, from its early roots to current applications, challenges, and future prospects. This allowed for the identification of rare variants in genes beyond APP, PSEN1 and PSEN2. Polygenic risk scores, which take into account multiple genetic variants associated with Alzheimer's disease, provide a more comprehensive assessment of genetic risk. Genetic testing can provide individuals and their healthcare providers with information about their genetic risk for AD, allowing for personalized risk assessments and interventions. Genetic markers can be used in conjunction with clinical assessments to aid in the early diagnosis of AD, potentially allowing for earlier interventions and better outcomes. Precision medicine approaches aim to match AD patients with the most appropriate treatments based on their genetic profile. This can involve selecting medications or interventions that target specific molecular pathways implicated in the disease [5].

Genetic testing can be used to identify eligible participants for clinical trials of new AD therapies. It allows researchers to enroll individuals who are more likely to benefit from experimental treatments. AD genetic testing often involves genetic counseling to help individuals and their families understand the implications of genetic results and make informed decisions about their healthcare and future planning. Genetic risk factors provide estimates of risk but do not guarantee the development of AD. Individuals with high-risk genetic profiles may not develop the disease, while those with low-risk profiles can still be affected. AD genetic testing raises ethical concerns related to informed consent, patient autonomy, and the potential psychological and emotional impact of genetic results. Ensuring the privacy and security of genetic data is essential to protect individuals from potential discrimination and breaches of confidentiality. Not all individuals have equal access to genetic testing, leading to potential disparities in care and the diagnosis of AD. The clinical utility of genetic testing in AD care is still evolving. While it holds promise, there is a need for further research to demonstrate its effectiveness in improving patient outcomes. Ongoing research aims to identify novel genetic biomarkers and therapeutic targets for AD. This may lead to the development of more precise treatments and interventions [6].

Conclusion

As our understanding of AD genetics deepens, interventions aimed at preventing or delaying the onset of the disease may become a reality. Early intervention strategies may include lifestyle modifications, personalized medications, or gene-based therapies. Genetic data will play an integral role in tailoring treatment plans for AD patients. This may involve selecting the most appropriate medications, dosages, and therapeutic approaches based on an individual's genetic profile. Genetic testing will empower patients to take a more active role in their healthcare decisions. It will facilitate informed choices about AD risk reduction strategies and early interventions. The evolution of genetic testing in Alzheimer's disease care has ushered in a new era of precision medicine. From early insights into familial forms of the disease to the discovery of numerous genetic risk factors, genetic testing has become a powerful tool in risk assessment, early diagnosis, treatment selection, and clinical trial recruitment. While challenges related to predictive uncertainty, ethics, and access persist, ongoing research and technological advancements hold promise for the future. As we continue to unravel the genetic complexities of Alzheimer's disease, genetic testing will play an increasingly pivotal role in providing personalized care and improving the lives of individuals affected by this devastating condition.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Muto, Masahiro, Yasuyoshi Kanari, Eiko Kubo and Tamami Takabe, et al. "Targeted disruption of Np95 gene renders murine embryonic stem cells hypersensitive to DNA damaging agents and DNA replication blocks." J Biol Chem 277 (2002): 34549-34555.

Google Scholar, Crossref, Indexed at

2. Karagianni, Panagiota, Larbi Amazit, Jun Qin and Jiemin Wong. "ICBP90, a novel methyl K9 H3 binding protein linking protein ubiquitination with heterochromatin formation." Mol Cell Biol 28 (2008): 705-717.

Google Scholar, Crossref, Indexed at

3. Vaissière, Thomas, Carla Sawan and Zdenko Herceg. "Epigenetic interplay between histone modifications and DNA methylation in gene silencing ." Mutat Res Rev Mutat Res 659 (2008): 40-48.

Google Scholar, Crossref, Indexed at

4. Bostick, Magnolia, Jong Kyong Kim, Pierre-Olivier Estève and Amander Clark, et al. "UHRF1 plays a role in maintaining DNA methylation in mammalian cells." Sci 317 (2007): 1760-1764.

Google Scholar, Crossref, Indexed at

5. Szyf, Moshe. "The DNA methylation machinery as a target for anticancer therapy." Pharmacol Ther 70 (1996): 1-37.

Google Scholar, Crossref, Indexed at

6. Weake, Vikki M. and Jerry L. Workman. "Histone ubiquitination: Triggering gene activity." Mol cell 29 (2008): 653-663.

Google Scholar, Crossref, Indexed at