Serum Calreticulin Acts as a Negative Biomarker in Alzheimer’s Disease Patients

Stefano Martino^*
*Correspondence: Stefano Martino, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy, Email:

Introduction

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment and a variety of behavioural changes. As the most common form of dementia, AD poses significant challenges to affected individuals, their families and healthcare systems worldwide. The pathophysiology of Alzheimer ’s disease is complex and multifaceted, involving the accumulation of amyloid-beta plaques, tau protein tangles, neuroinflammation and oxidative stress. The search for reliable biomarkers to aid in the early diagnosis and monitoring of AD has become a focal point in both clinical and research settings. Recent studies have identified calreticulin, a multifunctional protein found in the endoplasmic reticulum, as a potential biomarker for various diseases, including Alzheimer’s. Calreticulin plays a critical role in calcium homeostasis, protein folding and cellular signaling. Its involvement in neurodegenerative processes has been increasingly recognized, particularly its dual role in cell survival and apoptosis [1].

As researchers delve into the molecular mechanisms underpinning Alzheimer’s, the exploration of calreticulin’s function has gained traction, especially in the context of its potential as a negative biomarker in AD.A negative biomarker typically indicates the absence of a pathological condition or correlates inversely with disease severity. In the case of Alzheimer’s Disease, emerging evidence suggests that alterations in serum calreticulin levels may reflect underlying neurodegenerative processes. While higher levels of calreticulin have been associated with certain diseases, its reduced presence in the serum of AD patients raises intriguing questions about its role in disease pathology and progression. Understanding this relationship could have significant implications for early detection, therapeutic intervention and disease monitoring. The objective of this comprehensive analysis is to explore the relationship between serum calreticulin levels and Alzheimer ’s disease, examining how alterations in this protein may serve as a negative biomarker. This investigation will encompass the molecular biology of calreticulin, its known roles in neurobiology and the clinical implications of its serum levels in Alzheimer’s patients [2].

Description

Calreticulin is a 46 kDa calcium-binding chaperone primarily located within the endoplasmic reticulum. It plays several critical roles, including assisting in the proper folding of newly synthesized proteins and regulating intracellular calcium levels. The protein comprises several functional domains that facilitate its interaction with other proteins, including lectin-like domains that bind carbohydrates and calcium-binding motifs. Beyond its classical role in protein folding, calreticulin has been implicated in various cellular processes such as apoptosis, immune response regulation and intracellular signaling. In the context of neurodegeneration, calreticulin has been observed to mediate cellular responses to stress, contributing to cell survival or death depending on the context of its expression and localization. The connection between calreticulin and Alzheimer’s Disease has been explored through various avenues of research [3].

Studies suggest that calreticulin levels may change in response to the neurodegenerative processes characteristic of AD. For instance, calreticulin is believed to play a role in the cellular response to amyloid-beta toxicity, which is a hallmark of AD pathology. Elevated levels of calreticulin may initially serve a protective function; however, prolonged exposure to neurotoxic environments can lead to dysregulation and subsequent apoptosis. Moreover, the reduction of calreticulin in the serum of Alzheimer’s patients suggests a possible disruption in cellular homeostasis and stress responses. This could indicate a shift from protective to pathological mechanisms, thus marking a critical transition in disease progression. Understanding how these changes manifest in serum levels could pave the way for the development of diagnostic tools and therapeutic strategies targeting calreticulin pathways [4].

Investigating serum calreticulin levels in Alzheimer’s patients may provide insights into the disease's progression and offer potential for use as a biomarker. Current diagnostic methods for AD largely rely on clinical assessment and neuroimaging, often lacking sensitivity in the early stages. By identifying serum calreticulin as a negative biomarker, clinicians could leverage its levels to aid in the diagnosis and monitoring of Alzheimer’s, particularly in distinguishing it from other forms of dementia. Furthermore, the potential utility of serum calreticulin as a biomarker extends beyond diagnosis. Monitoring calreticulin levels could also assist in assessing treatment responses and disease progression, ultimately contributing to more personalized therapeutic approaches for individuals with Alzheimer’s Disease [5].

Conclusion

In conclusion, the investigation of serum calreticulin as a negative biomarker in Alzheimer’s Disease holds promise for enhancing our understanding of the disease's pathophysiology and improving clinical outcomes. As a protein involved in critical cellular processes, calreticulin's altered serum levels in AD patients may reflect underlying neurodegenerative changes and contribute to a more nuanced understanding of disease mechanisms. The exploration of calreticulin not only underscores the need for further research into its role within neurodegeneration but also highlights the potential for developing innovative diagnostic and therapeutic strategies that leverage biomarker profiles. As the field of Alzheimer’s research continues to evolve, identifying reliable biomarkers like serum calreticulin will be essential for advancing early diagnosis, monitoring disease progression and ultimately improving the quality of life for those affected by this devastating disorder.

Acknowledgement

None.

Conflict of Interest

No potential conflict of interest was reported by the authors.

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