## 4 Discussion
However, the changes in PEDF content in AD are controversial [27]. The PEDF is reduced in AD, according to a study conducted by [PERSON] and his colleagues [28]. The PEDF content in AD was also unchanged according to [PERSON] et al. and [PERSON] et al. [29, 30]. PEDF needs to be studied further to understand its effects on AD and AMPH-add [31]. Compared to control healthy subjects, AMPH-adds had a significant increase in MIP-4. [PERSON] and his colleagues observed similar findings by reporting that CCL18 plasma levels correlate with more severe inflammatory and neurodegenerative outcomes in multiple sclerosis [32]. According to [PERSON] and [PERSON], amphetamine-induced toxicity could be explained by its links to excitotoxicity (excess glutamate release), mitochondrial dysfunction, blood-brain barrier dysfunction, inflammation, and DNA damage. These factors explain, at a cellular level, the harmful effects of AMPH-add [33]. [PERSON] and his colleagues reported that AD-derived brain microvessels release high MIP protein and mRNA levels compared to controls; furthermore, oxidative and lipid insults to the brain microvasculature potentially contribute to the inflammatory environment in the AD brain [32]. Chemokine ligands and co-stimulatory factors are engaged in macrophage activation and differentiation processes, which may have a role in developing [PERSON]'s disease [33]. Cytokines and chemokines can also activate microglia and astrocytes (AC), increasing cytokine and chemokine expression. Reactivated microglia might engulf the debris of injured tissue and the deposition of AC as phagocytes in the CNS. AC that has been reactivated also plays a significant function. AC plays several functions in the onset and progression of Alzheimer's disease [34]. On the one hand, AC may phagocytose trash, offer food, and aid in controlling the chemical composition of the fluid surrounding neurons. On the other hand, AC promotes inflammation and is implicated in the creation of free radicals (FR) and intracellular neurofibrillary tangles, all of which contribute to the progression of AD [35]. Because AC is involved in the internalization, degradation, and generation of AB, its effects on AB are more complicated and controversial [36]. The association between serum-based liver function indicators and neurodegenerative biomarkers was explored in this study. The findings of this study revealed that the lower levels of ALT and higher AST to ALT ratio seen in amphetamine users were linked to AD biomarkers as well. In addition, an elevated AST to ALT ratio was linked to a higher PEDF level. In addition, a lower level of ALT was linked to a lower level of PEDF [37]. In patients with Alzheimer's disease, lower ALT and higher AST to ALT ratio values were found, which were linked to worsened memory and executive function scores [37]. The results of this investigation are similar to those of a previous study [38], which found higher AST to ALT ratio values and lower ALT levels in patients with AD compared to controls. In addition, changes in liver enzymes lead to abnormalities in liver-associated metabolites such as branched-chain amino acids, ether-phosphatidylcholines, and lipids, which are changed in AD and may have a role in disease pathophysiologic features, according to [PERSON] and colleagues [39]. PEDF is thought to be mostly derived from the liver [40, 41]. According to the data published by [PERSON] and colleagues, altered liver function indicators and amyloid-, tau-, and neurodegenerative biomarkers of AD pathogenesis appeared to be related to AD diagnosis and reduced memory and executive function [42]. The researchers discovered that a higher AST to ALT ratio and lower ALT levels were connected to the diagnosis of [PERSON]'s disease [42]. According to the researchers, higher AST to ALT ratio values were also linked to lower CSF levels of amyloid, and they increased amyloid deposition and CSF levels of PEDF [43; 44]. Lower ALT levels have also been linked to increased amyloid deposition and brain shrinkage [42].