Umoh Idiongo Okon, Dos Reis Helton Jose, de Oliveira Antonio Carlos Pinheiro
Departamento de Farmacologia, Instituto de Ciências Biológicas, Federal University of Minas Gerais, Av. Antonio Carlos 6627, Belo Horizonte 31270-901, MG, Brazil.
Int J Mol Sci. 2024 Mar 6;25(5):3044. doi: 10.3390/ijms25053044.
Alzheimer's disease (AD) is a progressive neurodegenerative disease mostly affecting the elderly population. It is characterized by cognitive decline that occurs due to impaired neurotransmission and neuronal death. Even though deposition of amyloid beta (Aβ) peptides and aggregation of hyperphosphorylated TAU have been established as major pathological hallmarks of the disease, other factors such as the interaction of genetic and environmental factors are believed to contribute to the development and progression of AD. In general, patients initially present mild forgetfulness and difficulty in forming new memories. As it progresses, there are significant impairments in problem solving, social interaction, speech and overall cognitive function of the affected individual. Osteoarthritis (OA) is the most recurrent form of arthritis and widely acknowledged as a whole-joint disease, distinguished by progressive degeneration and erosion of joint cartilage accompanying synovitis and subchondral bone changes that can prompt peripheral inflammatory responses. Also predominantly affecting the elderly, OA frequently embroils weight-bearing joints such as the knees, spine and hips leading to pains, stiffness and diminished joint mobility, which in turn significantly impacts the patient's standard of life. Both infirmities can co-occur in older adults as a result of independent factors, as multiple health conditions are common in old age. Additionally, risk factors such as genetics, lifestyle changes, age and chronic inflammation may contribute to both conditions in some individuals. Besides localized peripheral low-grade inflammation, it is notable that low-grade systemic inflammation prompted by OA can play a role in AD pathogenesis. Studies have explored relationships between systemic inflammatory-associated diseases like obesity, hypertension, dyslipidemia, diabetes mellitus and AD. Given that AD is the most common form of dementia and shares similar risk factors with OA-both being age-related and low-grade inflammatory-associated diseases, OA may indeed serve as a risk factor for AD. This work aims to review literature on molecular mechanisms linking OA and AD pathologies, and explore potential connections between these conditions alongside future prospects and innovative treatments.
阿尔茨海默病（AD）是一种主要影响老年人群的进行性神经退行性疾病。其特征是由于神经传递受损和神经元死亡而导致的认知能力下降。尽管淀粉样β（Aβ）肽的沉积和过度磷酸化TAU的聚集已被确认为该疾病的主要病理标志，但遗传和环境因素的相互作用等其他因素也被认为与AD的发生和发展有关。一般来说，患者最初表现为轻度健忘和难以形成新记忆。随着病情进展，患者在解决问题、社交互动、言语及整体认知功能方面会出现明显障碍。骨关节炎（OA）是最常见的关节炎形式，被广泛认为是一种全关节疾病，其特征是关节软骨进行性退变和侵蚀，伴有滑膜炎和软骨下骨改变，可引发外周炎症反应。OA也主要影响老年人，常累及膝关节、脊柱和髋关节等负重关节，导致疼痛、僵硬和关节活动度降低，进而严重影响患者的生活质量。由于多种健康问题在老年人中很常见，这两种疾病可能因独立因素而在老年人中同时出现。此外，遗传、生活方式改变、年龄和慢性炎症等风险因素可能在某些个体中导致这两种疾病。除了局部外周低度炎症外，值得注意的是，OA引发的低度全身炎症可能在AD发病机制中起作用。研究已经探讨了肥胖、高血压、血脂异常、糖尿病等全身炎症相关疾病与AD之间的关系。鉴于AD是最常见的痴呆形式，且与OA有相似的风险因素——两者均与年龄相关且与低度炎症相关疾病，OA可能确实是AD的一个风险因素。这项工作旨在综述关于连接OA和AD病理的分子机制的文献，并探讨这些疾病之间的潜在联系以及未来前景和创新治疗方法。
