Experimental gerontology最新文献

{"title":"Immunomodulatory and antioxidant effect of liposomal auraptene against cyclophosphamide-induced immunosuppression in BALB/c mice","authors":"","doi":"10.1016/j.exger.2024.112552","DOIUrl":"10.1016/j.exger.2024.112552","url":null,"abstract":"<div><h3>Introduction</h3><p>Cyclophosphamide (CP), which is a commonly used chemotherapy drug, can lead to a range of side effects such as immunosuppression, bone marrow suppression, leukopenia, and oxidative stress. This study aims to explore the effects of Auraptene (AUR), which has immunomodulatory and antioxidant properties, on immune function in mice that are experiencing suppression induced by CP.</p></div><div><h3>Materials and methods</h3><p>The experiment involved 60 male BALB/c mice that underwent a 10-day treatment. On days 1, 3, and 9, CP was given at 80 mg/kg IP doses to induce immunosuppression. The mice were divided into five groups: Control group, CP group, CP + liposomal AUR 0.2 mg/kg (AUR 0.2), CP + liposomal AUR 0.25 mg/kg (AUR 0.25), and liposomal vehicle group. Various parameters were measured, including mouse weight, immune organ weight index (spleen and thymus), spleen and thymus histopathology, levels of inflammatory cytokines (IL2, IL10, IL4, IFN-γ), TH1/TH2 balance ratio, IgG and IgM immunoglobulin levels, white blood cell count, platelets, neutrophils, lymphocytes, and oxidative activity measured by MDA, SOD, and Total Antioxidant.</p></div><div><h3>Results</h3><p>In the group treated with CP, the mice showed a significant decrease in weight compared to the control group. In contrast, the group treated with AUR maintained their weight and did not show a significant difference from the control group. AUR 0.25 reduced the damage to the spleen and thymus caused by CP. Additionally, AUR 0.25 demonstrated a significant decrease in IL4 and IL10 levels compared to the CP group (<em>p</em> = 0.04), approaching the levels of the control group. Furthermore, IL2 and IFN-γ levels in the AUR 0.25 group significantly increased (<em>p</em> = 0.04) compared to the CP group, reaching levels similar to the control group. AUR also increased serum IgM and IgG levels two to three times compared to the CP group, approaching the levels of the control group. MDA levels in the AUR 0.25 group decreased to normal and control levels. AUR 0.25 also showed increased SOD and Total Antioxidant levels. Additionally, white blood cells, platelets, neutrophils, and lymphocytes in the AUR group significantly increased compared to the CP group, reaching normal levels similar to the control group. The TH1/TH2 ratio in the AUR group exhibited a significant increase of two and a half times (<em>p</em> = 0.002) compared to the CP group.</p></div><div><h3>Conclusion</h3><p>These results show that AUR protects against the side effects of CP by increasing the function of the humoral and cellular immune system through the balance of TH1/TH2 and increasing the level of immunoglobulins, as well as increasing the antioxidant activity and the protective role of cytotoxicity.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524001980/pdfft?md5=ea91d8b82772d0ef3c483ff228864460&pid=1-s2.0-S0531556524001980-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of fibroblast autophagy and proliferation in skin anti-aging","authors":"","doi":"10.1016/j.exger.2024.112559","DOIUrl":"10.1016/j.exger.2024.112559","url":null,"abstract":"<div><p>Skin, as the outermost protective barrier of the body, becomes damaged with age and exposure to external stimuli. Dermal fibroblasts age and undergo apoptosis, which decreases collagen, collagen fibers, elastic fibers, hyaluronic acid, etc., leading skin to loss of elasticity and appearance of wrinkles. Skin aging is complex, involving several biological reactions，and various treatment methods are used to treat it. This review focuses on the importance of autophagy and cell proliferation in skin anti-aging, summarizes research progress on skin anti-aging by regulating autophagy and promoting the proliferation of dermal fibroblasts, and discusses future directions on skin anti-aging research.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524002055/pdfft?md5=28802c786051570056d15cfafda31cd0&pid=1-s2.0-S0531556524002055-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TDP-43 ameliorates aging-related cartilage degradation through preventing chondrocyte senescence","authors":"","doi":"10.1016/j.exger.2024.112546","DOIUrl":"10.1016/j.exger.2024.112546","url":null,"abstract":"<div><p>Senescent chondrocytes or signaling mechanisms leading to senescence are promising new therapeutic approaches for ameliorating cartilage degradation. Herein, we show that the transactive response DNA/RNA-binding protein (TDP-43) regulates chondrocyte senescence and ameliorates cartilage degradation. First, a significant decrease in TDP-43 was observed in 16-month-old mice compared with younger mice. Immunohistochemistry (IHC) analysis of mouse articular cartilage showed that p21, p16, p53, and matrix metalloprotein-13 (MMP13) were increased, but laminB1 and Collagen type II alpha1 1 chain (Col2a1) were decreased in 16-month-old mice. Furthermore, TDP-43 levels were decreased <em>in vivo</em> following D-galactose (D-gal) induction. Therefore, we investigated the role of TDP-43 in the senescent chondrocytes. ATDC5 cells were induced to overexpress TDP-43. Western blot analysis showed increased expression of laminB1, Ki67, and PCNA but decreased expression of p21, p16, p53, and MMP13. Senescence-associated-β-galactosidase (SA-β-Gal) assay, γH2AX staining, and EdU were performed to assess changes in chondrocytes, showing weaker SA-β-Gal and γH2AX staining but stronger EdU and Alican Blue staining. However, TDP-43 deficiency had opposing effects, and similar to D-gal stimulation results. Taken together, our data verified that TDP-43 negatively correlated with senescence markers, positively correlated with cell proliferation markers, and could alleviate cartilage degradation induced by D-gal. This may be an essential mechanism of cellular senescence and cartilage degradation.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S053155652400192X/pdfft?md5=a96b0944ef3f3f73dec29a12916fd0a8&pid=1-s2.0-S053155652400192X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytosterols in mountain cultivated ginseng, as master healthy ageing dietary supplement, activates steroid signaling in ageing Drosophila melanogaster","authors":"","doi":"10.1016/j.exger.2024.112554","DOIUrl":"10.1016/j.exger.2024.112554","url":null,"abstract":"<div><p>Mountain cultivated ginseng (MCG) is planted in mountain forests to simulate traditional wild ginseng; therefore, it has a greater pharmacological effect than cultivated ginseng (CG) in the garden; however, insufficient evidence confirms this theory. In light of the health-promoting and life-extending properties of ginseng, we analyzed the efficacy of MCG and CG. Initial observations revealed that the phytosterols content of MCG was higher than that of CG, with a positive correlation to the duration of growth. The distinction between phytosterols in MCG and in CG is predominately determined by the stigmasterol content using High-Performance Liquid Chromatography (HPLC). The lifespan of <em>Drosophila melanogaster</em> (fruit flies) that aged naturally was prolonged by phytosterols in MCG and CG and stigmasterols. Further, they prolonged healthy ageing as measured by progeny numbers, length of sleep, climbing distance, and survival following oxidative damage. The findings of behavioral observations revealed that phytosterols in MCG were more efficacious than in CG in promoting health maintenance and life extension; moreover, stigmasterol indicated that these effects were dose-dependent. Stigmasterols, phytosterols in MCG and CG have restored age-associated decreases in steroid hormone levels. Notably, molecular docking was predicted to promote stigmasterol's binding to the steroid hormone receptor ECR due to its similarity to steroid hormones. In addition, stigmasterols triggered the steroid hormone signaling pathway by increasing the activity of key genes <em>Eip75B</em> and <em>Br</em> in 20E signaling and <em>Jhamt</em>, <em>HmGR</em>, <em>Met</em>, and <em>Kr-h1</em> in JH signaling. Phytosterols, as a natural product, regulated health and longevity as a dietary supplement similar to that of steroids, which supported the social requirements of healthy ageing.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524002006/pdfft?md5=7b94096b556cac2a08911beafe03497c&pid=1-s2.0-S0531556524002006-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of asthma with the risk of cardiovascular disease: A Mendelian randomization study","authors":"","doi":"10.1016/j.exger.2024.112549","DOIUrl":"10.1016/j.exger.2024.112549","url":null,"abstract":"<div><h3>Background</h3><p>Association of asthma with the risk of cardiovascular disease has not been fully elucidated. So, this study tried to explore the genetic effect of asthma on five cardiovascular diseases and 90 peripheral cardiovascular proteins to answer the above topic.</p></div><div><h3>Methods</h3><p>Instrumental variables predicting asthma was extracted from its genome-wide association study data. Two-sample and multivariate MR approaches were used to assess the genetic association of exposure factor (i.e., asthma) with outcome factors (i.e., hypertension, atrial fibrillation, angina pectoris, myocardial infarction, heart failure, and 90 peripheral cardiovascular proteins).</p></div><div><h3>Results</h3><p>First, asthma nominally increased the risk of hypertension and atrial fibrillation (OR = 1.009, 95%CI = 1.003–1.016, <em>P</em> = 0.004; OR = 1.074, 95%CI = 1.024–1.127, <em>P</em> = 0.003). Second, of the 90 cardiovascular proteins, asthma was associated with the increased levels of tumor necrosis factor ligand superfamily member 14 and C<img>C motif chemokine 4 (β = 0.145, 95%CI = 0.077–0.212, <em>P</em> = 2.936e-05; β = 0.128, 95%CI = 0.063–0.193, <em>P</em> = 1.036e-04). Third, C<img>C motif chemokine 4 increased the risk of hypertension (<em>P</em> = 0.043); and after adjusting for this protein, asthma still increased the risk of hypertension, but the strength of its <em>P</em>-value changed from 0.004 to 0.011.</p></div><div><h3>Conclusion</h3><p>Asthma was a risk factor for hypertension and atrial fibrillation at the genetic level, and C<img>C motif chemokine 4 might play a mediating role in the mechanism by which asthma promoted hypertension. Thus, effective control of asthma may help reduce the risk of some cardiovascular diseases in older adults.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524001955/pdfft?md5=bba00354128e634d0917993928d5a3f2&pid=1-s2.0-S0531556524001955-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the causal relationship between frailty and sex hormone-binding globulin or insulin-like growth factor-1 levels: A sex-stratified bidirectional Mendelian Randomization study","authors":"","doi":"10.1016/j.exger.2024.112545","DOIUrl":"10.1016/j.exger.2024.112545","url":null,"abstract":"<div><h3>Background</h3><p>The association between frailty and sex hormone-binding globulin (SHBG) or insulin-like growth factor-1(IGF-1) levels demonstrates sex differences with inconsistent conclusions. This study aims to explore the causal relationship between frailty and SHBG or IGF-1 levels through bidirectional Mendelian randomization (MR).</p></div><div><h3>Methods</h3><p>We conducted two-sample bidirectional sex-stratified MR analyses using summary-level data from genome-wide association studies (GWASs) to examine the causal relationship between frailty and IGF-1 or SHBG levels, as measured by frailty index (FI) and frailty phenotype (FP). We use the random-effects inverse-variance weighted (IVW), weighted median, MR-Egger, MR-Egger intercept, and leave-one-out approaches.</p></div><div><h3>Result</h3><p>The relationship between frailty and SHBG or IGF-1 levels is inversely related, with a significant decrease in SHBG levels in females. Specifically, SHBG levels significantly decrease with FI (β = −5.49; 95 % CI: −9.67 to −1.32; FDR = 0.02) and more pronounced with FP (β = −10.14; 95 % CI: −16.16 to −4.13; FDR = 0.01), as determined by the IVW approach. However, reverse analysis shows no significant effect of IGF-1 or SHBG levels on either FI or FP (<em>p</em> &gt; 0.05).</p></div><div><h3>Conclusion</h3><p>Our study indicates a negative correlation between frailty and the levels of SHBG and IGF-1. It is suggested that further research is required to establish cut-off values for SHBG and IGF-1 levels in the frailty population. This is particularly important for females at higher risk, such as those undergoing menopause, to enable comprehensive assessment and early prevention efforts. While the findings imply that reduced IGF-1 and SHBG levels may not directly contribute to frailty, it is important not to overlook the underlying mechanisms through which they may indirectly influence frailty.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524001918/pdfft?md5=0e8c7d20fecf4184c34e66b3dfea6dc8&pid=1-s2.0-S0531556524001918-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in power and performance during sit-to-stand test and its relationships to functional measures in older adults with and without Parkinson's disease","authors":"","doi":"10.1016/j.exger.2024.112542","DOIUrl":"10.1016/j.exger.2024.112542","url":null,"abstract":"<div><h3>Aims</h3><p>i) to compare 30-s sit-to-stand (STS) test repetitions and power between older adults with and without Parkinson's disease (PD) and ii) to evaluate the relationship of STS repetitions and power with functional measures in older people with PD.</p></div><div><h3>Methods</h3><p>STS repetitions and power (Alcazar's equation) during the 30-s STS test were assessed in forty-six age- and sex-matched older adults with and without PD. Functional measures included habitual (HGS) and maximum gait speed (MGS), timed-up-and-go (TUG) test and the Mini-Balance Evaluation System Test (Mini-BEST). PD-specific tests were as follows: the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS-III), quality of life [Parkinson's Disease Questionnaire (PDQ-39)], perceived freezing of gait (FOG questionnaire), and fear of falling [Falls Efficacy Scale (FES)]. T scores, repeated measures ANOVA and linear regression analyses were used.</p></div><div><h3>Results</h3><p>T scores for older adults with PD were − 2.7 ± 4.5 for STS repetitions, −5.2 ± 4.2 for absolute STS power, and − 3.1 ± 4.6 for relative STS power compared to older adults without PD. T scores for absolute STS power were lower than T scores for STS repetitions (<em>p</em> &lt; 0.001) and relative STS power (<em>p</em> &lt; 0.001). Both absolute and relative STS power and STS repetitions showed similar correlations with functional measures (<em>r</em> = 0.44 to 0.59; both <em>p</em> &lt; 0.05). Relative STS power (<em>r</em> = −0.55; <em>p</em> &lt; 0.05) and STS repetitions (<em>r</em> = −0.47 to −0.55; <em>p</em> &lt; 0.05) but not absolute STS power were correlated to PD-specific tests.</p></div><div><h3>Conclusions</h3><p>STS repetitions and power values estimated through the 30-s STS test were lower in older people with PD than without PD. Overall, STS power measures were similarly associated with functional performance as STS repetitions, indicating these power equations can be implemented when assessing lower extremity function in older people with PD.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524001888/pdfft?md5=36875ae592d7f38c397037815e231bb8&pid=1-s2.0-S0531556524001888-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Aerobic exercise alleviates skeletal muscle aging in male rats by inhibiting apoptosis via regulation of the Trx system” [Exp. Gerontol. 194 (2024) 112523]","authors":"","doi":"10.1016/j.exger.2024.112541","DOIUrl":"10.1016/j.exger.2024.112541","url":null,"abstract":"","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524001876/pdfft?md5=a357c67b98d24e98721db8e67ef048b8&pid=1-s2.0-S0531556524001876-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between frailty and main work during the LIFE: A cross-sectional analysis of the UK Biobank","authors":"","doi":"10.1016/j.exger.2024.112548","DOIUrl":"10.1016/j.exger.2024.112548","url":null,"abstract":"<div><h3>Background</h3><p>The role of main work during the life course in predicting frailty, a typical geriatric syndrome, is still largely unknown. Therefore, with this research, we aimed to investigate the potential association between the main work done during the life with frailty and pre-frailty among participants 60 years and older of the UK Biobank study.</p></div><div><h3>Methods</h3><p>Frailty and pre-frailty presence were ascertained using a model including 5 indicators (weakness, slowness, weight loss, low physical activity, and exhaustion); the main employment status was ascertained using self-reported information. The association between frailty and main work was explored using an ordinal logistic regression model and reported as odds ratios (ORs) with their 95 % confidence intervals (CIs).</p></div><div><h3>Results</h3><p>The final sample comprised a total of 50,447 individuals (mean age: 64.2 years, females: 50.2 %). Individuals with higher qualifications had a reduced risk of frailty (OR = 0.881, 95%CI = 0.83–0.95, <em>p</em>-value&lt;0.001 for pre-frail and OR = 0.681, 95%CI = 0.63–0.73, p-value&lt;0.001 for frail) compared to those with lower qualifications. Moreover, active participation in the workforce, compared to being inactive, emerged as a protective factor from frailty (OR = 0.753, 95%CI = 0.70–0.81, <em>p</em>-value&lt;0.001). The categories of Associate Professional and Technical Occupations exhibited protective effects against both pre-frailty and frailty. Similarly, occupations categorized as Professional and Management demonstrated protective effects against pre-frailty and frailty when compared to Elementary Occupations. Additionally, engagement in Trades and Services occupations, as opposed to Elementary Occupations, appeared to be protective against frailty.</p></div><div><h3>Conclusions</h3><p>In this large cross-sectional investigation based on the data of the UK Biobank we found that work during lifetime could be an important factor in determining frailty later in life.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524001943/pdfft?md5=bf3a584f483d2b876603709ca1984799&pid=1-s2.0-S0531556524001943-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141993321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tau pathology mediated the plasma biomarkers and cognitive function in patients with mild cognitive impairment","authors":"","doi":"10.1016/j.exger.2024.112535","DOIUrl":"10.1016/j.exger.2024.112535","url":null,"abstract":"<div><p>Glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) are putative non-amyloid biomarkers indicative of ongoing inflammatory and neurodegenerative disease processes. Hence, this study aimed to demonstrate the relationship between plasma biomarkers (GFAP and NfL) and ¹⁸F-AV-1451 tau PET images, and to explore their effects on cognitive function. Ninety-one participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and 20 participants from the Shanghai Action of Prevention Dementia for the Elderly (SHAPE) cohort underwent plasma biomarker testing, ¹⁸F-AV-1451 tau PET scans and cognitive function assessments. Within the ADNI, there were 42 cognitively normal (CN) individuals and 49 with mild cognitive impairment (MCI). Similarly, in the SHAPE, we had 10 CN and 10 MCI participants. We calculated the standardized uptake value ratios (SUVRs) for the regions of interest (ROIs) in the ¹⁸F-AV-1451 PET scans. Using plasma biomarkers and regional SUVRs, we trained machine learning models to differentiate between MCI and CN subjects with ADNI database and validated in SHAPE.</p><p>Results showed that eight selected variables (including left amygdala SUVR, right amygdala SUVR, left entorhinal cortex SUVR, age, education, plasma NfL, plasma GFAP, plasma GFAP/ NfL) identified by LASSO could differentiate between the MCI and CN individuals, with AUC ranging from 0.783 to 0.926. Additionally, cognitive function was negatively associated with the plasma biomarkers and tau deposition in amygdala and left entorhinal cortex. Increased tau deposition in amygdala and left entorhinal cortex were related to increased plasma biomarkers. Moreover, tau pathology mediated the effect of plasma biomarkers level on the cognitive decline. The present study provides valuable insights into the association among plasma markers (GFAP and NfL), regional tau deposition and cognitive function. This study reports the mediation effect of brain regions tau deposition on the plasma biomarkers level and cognitive function, indicating the significance of tau pathology in the MCI patients.</p></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0531556524001773/pdfft?md5=fdc9027bb2ba98a4494449e584743294&pid=1-s2.0-S0531556524001773-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}