Department of Food and Drug, University of Parma, Parma, Italy.
Department of Medicine and Surgery, Unit of Neuroscience, University of Parma, Parma, Italy.
J Alzheimers Dis. 2024 Nov;102(1):162-172. doi: 10.1177/13872877241284213. Epub 2024 Oct 15.
Alterations in factors involved in cholesterol homeostasis are critical in Alzheimer's disease (AD), but the stage of occurrence, their specific association, and a possible relationship with the genotype are not clarified.
We aimed to quantify and correlate specific lipid factors in patients with different degrees of cognitive decline, namely patients with AD and patients with mild cognitive impairment due to AD (MCI-AD), carriers or non-carriers of the genotype.
We evaluated Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), cholesterol and the oxidative metabolites 24-, 25-, 27-hydroxycholesterol (HC) in the cerebrospinal fluid (CSF) and serum of AD (n = 28) and MCI-AD (n = 27) patients.
CSF and serum PCSK9 and lipids were similar, except for higher serum PCSK9 and triglycerides in MCI-AD compared to AD. In CSF, AD carriers showed higher PCSK9 and 24-HC (+61.3%, = 0.027 and +32.7%, = 0.037), compared to non-carriers. There was a negative association between CSF PCSK9 and 27-HC in AD (r = -0.444, = 0.049) and, exclusively among AD carriers, a negative association between CSF PCSK9 and 24-HC (r = -0.786, = 0.028). A positive correlation was observed between CSF and serum PCSK9 in AD (r = 0.520, = 0.004), driven by carriers (r = 0.544, = 0.038), suggesting PCSK9 exchange between brain and periphery. A positive correlation was detected between serum and CSF 27-HC (r = 0.465, = 0.039) in AD. None of these results were found in MCI-AD patients.
PCSK9 and 24-HC might be specific markers of ApoE4-associated lipid alterations in AD, possibly contributing to clinical progression in the AD continuum.
胆固醇稳态相关因子的改变在阿尔茨海默病（AD）中至关重要，但发生阶段、具体关联以及与 基因型的可能关系尚不清楚。
我们旨在量化和比较不同认知衰退程度患者的特定脂质因子，即 AD 患者和 AD 所致轻度认知障碍（MCI-AD）患者，以及 基因型的携带者或非携带者。
我们评估了前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（PCSK9）、胆固醇和脑脊液（CSF）及血清中的氧化代谢产物 24-、25-、27-羟基胆固醇（HC）在 AD（n=28）和 MCI-AD（n=27）患者中的含量。
CSF 和血清中的 PCSK9 和脂质相似，但 MCI-AD 患者的血清 PCSK9 和甘油三酯水平高于 AD 患者。在 CSF 中，与非携带者相比，AD 携带者的 PCSK9 和 24-HC 水平更高（分别增加 61.3%， = 0.027 和 32.7%， = 0.037）。AD 患者的 CSF PCSK9 与 27-HC 呈负相关（r=−0.444， = 0.049），且仅在 AD 携带者中，CSF PCSK9 与 24-HC 呈负相关（r=−0.786， = 0.028）。AD 患者的 CSF 和血清 PCSK9 之间存在正相关（r=0.520， = 0.004），这主要由携带者驱动（r=0.544， = 0.038），提示 PCSK9 在大脑和外周之间发生交换。AD 患者的血清和 CSF 27-HC 之间存在正相关（r=0.465， = 0.039）。在 MCI-AD 患者中未发现这些结果。
PCSK9 和 24-HC 可能是 AD 中 ApoE4 相关脂质改变的特异性标志物，可能有助于 AD 连续体中的临床进展。
