Nasme Fariha, Behera Jyotirmaya, Tyagi Prisha, Debnath Nabendu, Falcone Jeff C, Tyagi Neetu
Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
Division of Immunology, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
Biogerontology. 2025 Jan 20;26(1):43. doi: 10.1007/s10522-024-10181-z.
Alzheimer's disease (AD) and osteoporosis (OP) pose distinct but interconnected health challenges, both significantly impacting the aging population. AD, a neurodegenerative disorder characterized by memory impairment and cognitive decline, is primarily associated with the accumulation of abnormally folded amyloid beta (Aβ) peptides and neurofibrillary tangles in the brain. OP, a skeletal disorder marked by low bone mineral density, involves dysregulation of bone remodeling and is associated with an increased risk of fractures. Recent studies have revealed an intriguing link between AD and OP, highlighting shared pathological features indicative of common regulatory pathophysiological pathways. In this article, we elucidate the signaling mechanisms that regulate the pathology of AD and OP and offer insights into the intricate network of factors contributing to these conditions. We also examine the role of bone-derived factors in the progression of AD, underscoring the plausibility of bidirectional communication between the brain and the skeletal system. The presence of amyloid plaques in the brain of individuals with AD is akin to the accumulation of brain Aβ in vascular dementia, pointing towards the need for further investigation of shared molecular mechanisms. Moreover, we discuss the role of bone-derived microRNAs that may regulate the pathological progression of AD, providing a novel perspective on the role of skeletal factors in neurodegenerative diseases. The insights presented here should help researchers engaged in exploring innovative therapeutic approaches targeting both neurodegenerative and skeletal disorders in aging populations.
阿尔茨海默病(AD)和骨质疏松症(OP)带来了不同但相互关联的健康挑战,二者均对老年人群体产生重大影响。AD是一种以记忆障碍和认知衰退为特征的神经退行性疾病,主要与大脑中异常折叠的β淀粉样蛋白(Aβ)肽和神经原纤维缠结的积累有关。OP是一种以骨矿物质密度低为特征的骨骼疾病,涉及骨重塑失调,并与骨折风险增加有关。最近的研究揭示了AD与OP之间存在有趣的联系,突出了共同的病理特征,表明存在共同的调节病理生理途径。在本文中,我们阐明了调节AD和OP病理的信号机制,并深入探讨了促成这些病症的复杂因素网络。我们还研究了骨源因子在AD进展中的作用,强调了大脑与骨骼系统之间双向交流的合理性。AD患者大脑中淀粉样斑块的存在类似于血管性痴呆中大脑Aβ的积累,这表明需要进一步研究共同的分子机制。此外,我们讨论了可能调节AD病理进展的骨源微小RNA的作用,为骨骼因子在神经退行性疾病中的作用提供了新的视角。本文提出的见解应有助于研究人员探索针对老年人群体神经退行性和骨骼疾病的创新治疗方法。