Astrocyte Dysregulation and Calcium Ion Imbalance May Link the Development of Osteoporosis and Alzheimer’s Disease

Article type: Research Article

Authors: Tsai, Yi-Liang^{a; b; *} | Yen, Chieh-Tsung^c | Wang, Yuh-Feng^{a; d; e; f; *}

Affiliations: [a] Department of Nuclear Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan | [b] Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan | [c] Department of Neurology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan | [d] Department of Radiology, School of Medicine, Tzu Chi University, Hualien, Taiwan | [e] Center of Preventive Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan | [f] Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Correspondence: [*] Correspondence to: Yi-Liang Tsai, Department of Nuclear Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation No. 2, Minsheng Rd., Dalin Township, Chiayi 622, Taiwan, R.O.C. Tel.: +886 5 2648000/Ext. 5704; E-mail: [email protected] and Yuh-Feng Wang MD, PhD, No. 201, Sec. 2, Shipai Rd., Beitou Dist., Taipei City 112201, Taiwan, R.O.C. Tel.: +886 2 28757301/Ext. 500; E-mail: [email protected].

Abstract: The typical symptoms of patients with Alzheimer’s disease (AD) are amyloid-β (Aβ) plaques and tau hyperphosphorylation. However, recent studies show that these symptoms are not the cause of the disease but are generated after the pathogenesis. Compared with other types of dementia, AD has the obvious features of pineal gland calcification and decreased melatonin production. The pineal gland is mainly composed of pinealocytes that release melatonin and astrocytes. Astrocytes function to maintain a balanced concentration of calcium ions, provide nerve cell nutrients, and migrate nutrients in vivo. Calcium ions are among the most important neurotransmitters. Once triggered, a calcium wave can be formed between astrocytes to activate other astrocytes to transmit information. Most calcium is stored in the skeleton. Bone tissue is composed mainly of osteocytes, osteoblasts, and osteoclasts. Of these, osteocyte is a kind of astrocyte which regulates the activity of osteoclasts and osteoblasts. The pineal gland is composed mainly of astrocytes; osteocytes are also a kind of astrocyte. Therefore, we conclude that when astrocytes are gradually disabled, calcium may be lost from the bones, prompting osteoporosis. The calcium ions then released into the blood may accumulate and cause ectopic calcification in the pineal gland, which promotes the occurrence of AD. Finally, this study used aspects of drugs and hormones (bone and calcium metabolism hormones and melatonin) to infer the hypothesis, which proposes that astrocyte dysregulation promotes the long-term imbalance of calcium ions in vivo and leads to osteoporosis and AD.

Keywords: Alzheimer’s disease, astrocyte, bone, calcium ion, osteoporosis

DOI: 10.3233/JAD-220218

Journal: Journal of Alzheimer's Disease, vol. 88, no. 2, pp. 439-445, 2022