Department of Neurology, College of Medicine, University of Kentucky, Lexington, KY, United States of America.
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United States of America; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, United States of America.
Neurobiol Dis. 2023 Aug;184:106202. doi: 10.1016/j.nbd.2023.106202. Epub 2023 Jun 15.
Neurological conditions such as Alzheimer's disease (AD) and related dementias (ADRD) present with many challenges due to the heterogeneity of the related disease(s), making it difficult to develop effective treatments. Additionally, the progression of ADRD-related pathologies presents differently between men and women. With two-thirds of the population affected with ADRD being women, ADRD has presented itself with a bias toward the female population. However, studies of ADRD generally do not incorporate sex-based differences in investigating the development and progression of the disease, which is detrimental to understanding and treating dementia. Additionally, recent implications for the adaptive immune system in the development of ADRD bring in new factors to be considered as part of the disease, including sex-based differences in immune response(s) during ADRD development. Here, we review the sex-based differences of pathological hallmarks of ADRD presentation and progression, sex-based differences in the adaptive immune system and how it changes with ADRD, and the importance of precision medicine in the development of a more targeted and personalized treatment for this devastating and prevalent neurodegenerative condition.
由于相关疾病的异质性,阿尔茨海默病(AD)和相关痴呆症(ADRD)等神经疾病带来了许多挑战,使得难以开发有效的治疗方法。此外,ADRD 相关病理的进展在男性和女性之间表现不同。由于三分之二的 ADRD 患者为女性,ADRD 对女性群体存在偏见。然而,在研究 AD 的发展和进展时,一般的研究并未纳入基于性别的差异,这不利于理解和治疗痴呆症。此外,适应性免疫系统在 AD 发展中的作用最近也提出了新的需要考虑的因素,包括 AD 发展过程中免疫反应的性别差异。在这里,我们综述了 ADRD 表现和进展的病理特征的性别差异、适应性免疫系统的性别差异以及其如何随 ADRD 而变化,以及精准医学在开发更有针对性和个性化的治疗方法方面的重要性,以应对这种破坏性和普遍存在的神经退行性疾病。