International Clinical and Medical Case Reports Journal (ISSN: 2832-5788) | Volume 4, Issue 11 | Research Article | Open Access DOI

Carbon Dioxide–Calcium Crosstalk in Alzheimer’s Disease: A Mechanistic Model of Neurodegeneration

Abdelrazak Mansour Ali*

Abdelrazak Mansour Ali1*, Radwa Abdelrazak Ali2, Mohamed Abdeltawab Ibrahim3, Mohga Abdeltawab Barbar4

1Professor Dr. (MD, PhD), Corresponding Author, Professor of Pediatrics, International Center for Population Studies and Research, Al-Azhar University, Cairo, Egypt

2Associate Researcher, B.Sc. in Neuroscience (George Mason University), M.Sc. (University of Virginia), National Institutes of Health, Department of Research, USA

3Doctor of Medicine (MD), Ministry of Health, General Director of Marsa Alam Hospital, and Quality Management Consultant, Egypt

4Mohga Abdeltawab Barbar, B.Sc. and M.Sc., Agricultural Research Center, Ministry of Agriculture, Egypt

*Correspondence to: Abdelrazak Mansour Ali 

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Abstract

Background: The incidence of Alzheimer’s disease has risen in parallel with increasing atmospheric carbon dioxide (CO₂) levels over the past century.

Objective: To investigate whether elevated CO₂ levels are associated with Alzheimer’s disease. Design: A case-control study conducted at tertiary hospitals in Egypt.

Methods: A total of 78 patients diagnosed with Alzheimer’s disease and 45 age- and sex-matched controls (65–76 years old) were enrolled. All participants underwent clinical examination and completed a standardized questionnaire collecting demographic information, including age, sex, occupation, smoking status, family history, and history of chronic respiratory disease or occupational CO₂ exposure, in accordance with the National Institute for Occupational Safety and Health criteria (August 1976). Recruitment occurred between November 2023 and October 2024. Arterial blood gas analysis was performed for all participants, and selected patients underwent additional evaluations to confirm the diagnosis of Alzheimer’s disease, where applicable. PaCO₂ levels were analyzed using two independent statistical methods to assess significance.

Results: The mean PaCO₂ (± SD) was 46.20 ± 2.26 mmHg in patients with Alzheimer’s disease compared to 43.73 ± 3.02 mmHg in controls, with a standard error (SE) of 0.518 and a 95% confidence interval of 1.44–3.50 (P < 0.0001). Elevated PaCO₂ was observed in 54 (69.2%) cases and 9 (20.0%) controls (P < 0.00001).

Conclusion: This study demonstrates a significant association between elevated CO₂ levels and Alzheimer’s disease. The underlying mechanisms may involve CO₂-induced alterations in cell membrane integrity, calcium homeostasis, and intracellular signaling pathways. CO₂-related acidification may impair β-amyloid–clearing enzymes by disrupting zinc-binding histidine residues, thereby promoting Aβ accumulation, while its thermogenic effect may accelerate microtubule degradation and neuronal instability. These findings highlight CO₂-associated pathways as potential therapeutic targets, including strategies to limit CO₂ accumulation or diffusion and the use of hyperbaric oxygen therapy to mitigate CO₂-driven receptor modulation and neuroinflammation.

Keywords:

CO2; Ca2+; Alzheimer’s disease; Amyloid; Calcium

Citation:

Abdelrazak Mansour Ali, Radwa Abdelrazak Ali, Mohamed Abdeltawab Ibrahim, Mohga Abdeltawab Barbar. Carbon Dioxide–Calcium Crosstalk in Alzheimer’s Disease: A Mechanistic Model of Neurodegeneration. Int Clinc Med Case Rep Jour. 2025;4(11):1-20.