Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that deteriorates cognitive function. Patients with AD generally exhibit neuroinflammation, elevated beta-amyloid (Aβ), tau phosphorylation (p-tau), and other pathological changes in the brain. The kynurenine pathway (KP) and several of its metabolites, especially quinolinic acid (QA), are considered to be involved in the neuropathogenesis of AD. The important metabolites and key enzymes show significant importance in neuroinflammation and AD. Meanwhile, the discovery of changed levels of KP metabolites in patients with AD suggests that KP metabolites may have a prominent role in the pathogenesis of AD. Further, some KP metabolites exhibit other effects on the brain, such as oxidative stress regulation and neurotoxicity. Both analogs of the neuroprotective and antineuroinflammation metabolites and small molecule enzyme inhibitors preventing the formation of neurotoxic and neuroinflammation compounds may have potential therapeutic significance. This review focused on the KP metabolites through the relationship of neuroinflammation in AD, significant KP metabolites, and associated molecular mechanisms as well as the utility of these metabolites as biomarkers and therapeutic targets for AD. The objective is to provide references to find biomarkers and therapeutic targets for patients with AD.

This study was designed to evaluate the microstructural integrity of white matter (WM) in amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD) among Han Chinese elderly using diffusion tensor imaging (DTI) technique, and to investigate the relationship between WM abnormalities and cognitive dysfunction. Sixty-four subjects (23 mild probable AD, 20 amnestic MCI, and 21 age-matched normal controls) who did not have visible WM lesion burden were analyzed. Fractional anisotropy (FA) and mean diffusivity were measured in normal-appearing WM (NAWM) using DTI with 64 encoding directions. The results were correlated with the scores of Mini-Mental State Examination (MMSE) and Cognitive Ability Screening Instrument (CASI). Statistical analysis showed the FA value in parietal WM was significantly lower in MCI compared to NC (P<0.001), and further decreased in AD compared to MCI (P=0.005). The lower FA and elevated mean diffusivity values were found in temporal WM, frontal WM, parahippocampal and posterior cingulate fibers of AD group compared to MCI and NC (all P<0.01). Canonical correlation analysis showed that the parietal FA values measured from all subjects were significantly correlated with the scores of CASI and MMSE (P<0.01). The results indicated that DTI can detect microstructural WM abnormalities in AD and amnestic MCI, and the measures were correlated with cognitive performance. In MCI, the abnormality was found to be limited within the parietal WM; and in AD a more widespread alteration was found in other brain regions as well.

Background A number of studies have explored the association between depression and ghrelin, leptin, and cortisol; further, postprandial C-peptide levels have a therapeutic effect on type 2 diabetes mellitus (T2DM). However, the relationship between C-peptide and depression in patients with diabetes, remains unclear. The aim of this study was to explore the association between depression and ghrelin, leptin, cortisol, and C-peptide in patients with diabetes. Methods We enrolled 50 adults without T2DM, 77 non-depressed adults with T2DM (free of Axis-I psychiatric disorders as assessed using the Mental Illness Needs Index (MINI), Patient Health Questionnaire (PHQ-9 score ≤ 4)) and 59 patients with T2DM and depression (PHQ-9 ≥ 7 and positive by the Structured Clinical Interview for DSM-5). The age range of the participants was 45–59 years of age. We compared the above three groups and explored the association between ghrelin, leptin, cortisol, C-peptide, and depression in patients with diabetes. A post-hoc power-analysis was finished. Results Compared with the non-depression T2DM group, the depression T2DM group had significantly higher blood glucose fluctuations. Further, compared with the non-depression T2DM and non-diabetic groups, the depression T2DM group had significantly lower levels of post-meal 2-h C-peptide and elevated evening cortisol (p < 0.01). Regression analysis revealed a significant negative correlation between depression severity and 2-h postprandial C-peptide in patients with diabetes (p < 0.01) and a significant positive correlation with midnight cortisol levels (p < 0.01). A post hoc power analysis showed that we had an adequate sample size and met the minimum requirement to attain 80% power. A post hoc power calculation also demonstrated that this study basically achieved power of 80% at 5% alpha level. Conclusions Our findings indicate a correlation of low fasting levels of 2-h C-peptide as well as higher midnight cortisol levels with higher depression severity in middle-aged patients with T2DM.

Many previous studies have noticed obvious alterations in different white matter tracts among patients with major depressive disorder (MDD). Growing evidence also strongly suggest a role of leptin in the pathogenesis of MDD, but with conflicting results of leptin levels. However, no previous studies have examined the relationship between leptin and white matter integrity of patients with MDD. Therefore, we aimed in this study to investigate the relationship between white matter alterations and plasma leptin levels in both drug-naïve and medicated MDD patients. We measured plasma leptin levels and white matter integrity using diffusion tensor imaging (DTI) and voxel-based analysis (VBA) in 140 participants (40 drug-naïve MDD patients; 40 medicated MDD patients; 60 healthy controls) aged between 18 and 49 years old. A significant reduced fractional anisotropy (FA) value in the dorsomedial thalamus was found for both drug-naïve and medicated MDD patients compared to the healthy non-depressed participants ( p < 0.01, corrected). In addition, leptin levels were significantly higher in the drug-naïve MDD patients and were negatively correlated with the detected white matter alteration. Our results suggest that the elevated plasma leptin levels in the drug-naïve MDD group might be associated with the changes of the white matter integrity in the dorsomedial thalamus region.