Darabi Shahram, Gorgich Enam Alhagh Charkhat, Moradi Fatemeh, Rustamzadeh Auob
Cellular and Molecular Research Center, Research Institute for Prevention of Non-communicable Diseases, Department of Anatomical Sciences, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Department of Anatomy, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran.
IBRO Neurosci Rep. 2025 Jan 9;18:191-199. doi: 10.1016/j.ibneur.2025.01.004. eCollection 2025 Jun.
Amyloid-beta (Aβ) production is a normal physiological process, essential for neuronal function. However, an imbalance in Aβ production and clearance is the central pathological feature of Alzheimer's disease (AD), leading to the accumulation of Aβ plaques in the brain. Low-density lipoprotein receptor-related protein 1 (LRP1) plays a critical role in both the central clearance of Aβ from the brain and its peripheral transport to visceral organs. Disruptions in these processes contribute to the accumulation of Aβ in the central nervous system (CNS) and the progression of AD. Recent research emphasizes the need for a broader focus on the systemic effects of organs outside the brain, particularly in the context of AD prevention and treatment. The contribution of peripheral systems, such as the liver, in Aβ clearance, is vital, given that Aβ levels in the plasma correlate closely with those in the brain. Consequently, targeting systemic processes, rather than focusing solely on the CNS, may offer promising therapeutic approaches. Furthermore, high-density lipoprotein (HDL) facilitates the formation of lipoprotein-amyloid complexes, which are important for Aβ transport and clearance, using proteins such as apolipoproteins E and J (ApoE and ApoJ) to form complexes that help manage Aβ accumulation. On the other hand, low-density lipoprotein (LDL) facilitates Aβ efflux from the brain by binding to LRP1, promoting its clearance. Given the relationship between lipid profiles and Aβ levels, along with lipid-modifying drugs, may be effective in managing Aβ accumulation and mitigating AD progression.
淀粉样β蛋白（Aβ）的产生是一个正常的生理过程，对神经元功能至关重要。然而，Aβ产生与清除的失衡是阿尔茨海默病（AD）的核心病理特征，导致大脑中Aβ斑块的积累。低密度脂蛋白受体相关蛋白1（LRP1）在Aβ从大脑的中枢清除及其向内脏器官的外周转运中均起关键作用。这些过程的紊乱会导致Aβ在中枢神经系统（CNS）中的积累以及AD的进展。最近的研究强调，需要更广泛地关注大脑以外器官的全身效应，特别是在AD预防和治疗的背景下。鉴于血浆中Aβ水平与大脑中的Aβ水平密切相关，外周系统（如肝脏）在Aβ清除中的作用至关重要。因此，针对全身过程，而不是仅关注中枢神经系统，可能会提供有前景的治疗方法。此外，高密度脂蛋白（HDL）利用载脂蛋白E和J（ApoE和ApoJ）等蛋白质促进脂蛋白 - 淀粉样蛋白复合物的形成，这些复合物对于Aβ的转运和清除很重要，有助于控制Aβ的积累。另一方面，低密度脂蛋白（LDL）通过与LRP1结合促进Aβ从大脑中流出，促进其清除。鉴于脂质谱与Aβ水平之间的关系，连同脂质修饰药物可能有效地控制Aβ的积累并减轻AD的进展。
