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

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.

Bone Tissue and the Nervous System: What Do They Have in Common?

“…In AD, bone mass reduction, characterized by the increase in inflammatory markers, can be considered a risk factor [13]. Recently, it has been reported that astrocyte alterations and an imbalance in calcium levels link osteoporosis and AD [142]. Moreover, AD causes beta amyloid accumulation in the bone, promoting RANKL-induced osteoclastic activation and thus favoring bone resorption [143].…”

Transcriptomic network analysis of brain and bone reveals shared molecular mechanisms underlying Alzheimer’s Disease and related dementias (ADRD) and Osteoporosis

“…On a molecular level, several mechanisms have been shown to contribute to the pathophysiology of OP and ADRD. These mechanisms include oxidative stress [7], accumulation of advanced glycation end products (AGEs) [8], calcification [9], calcium ion imbalance [10], immunological factors such as cytokine secretion [11][12][13], defects in glucose uptake [14], endoplasmic reticulum-stress driven senescence [15], endogenous or exogenous estrogen exposure [16][17][18][19], vitamin D signaling [20,21], receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) signaling [22], and Wnt/β-catenin signaling [23][24][25]. Bone metabolic markers have shown association with AD outcomes, including serum osteocalcin, osteopontin, and sclerostin, and urine deoxypyridinoline/creatinine ratio and calcium/creatinine ratio [26][27][28][29][30].…”