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Background: Endoplasmic reticulum (ER) stress is considered as a central pathophysiology for neurodegeneration in Alzheimer's disease (AD). Many studies using in vitro cell line or in vivo mouse model have shown the possible association between ER stress and neurodegeneration. However, that connection was not elucidated well in AD patient‐derived cell or brain organoids. In this study, we aimed to identify transcriptional regulation landscape and potential therapeutic targets against ER stress using AD dementia patient‐derived dermal fibroblast. Method: For the purposes of ex vivo research, we performed skin biopsy and stabilized dermal fibroblasts in vitro. Total of 20 AD dementia patients and 22 cognitively normal older adults were assessed. All of AD dementia patients were amyloid positive on PET imaging, APOE e4 carrier, and cognition was imparied. On the contrary, all of cognitively normal older adults were amyloid negative on PET imaging, and APOE e4 non‐carrier. We applied thabsigargin (10 nM) to dermal fibroblast for 24 hours to promote ER stress. After that, to identify transcriptional regulation landscape against ER stress, RNA sequencing was performed. Result: Total of 252 transcripts (up = 162, down = 90) were commonly differentially expressed in both of AD dementia and cognitively normal older adults derived dermal fibroblast by ER stress‐thabsigargin. These transcripts were enriched in GO categories related to protein folding in ER, response to ER stress, and ERAD pathway. Interestingly, 80 transcripts (up = 33, down = 47) were only differentially expressed in AD dementia dermal fibroblast by ER stress‐thabsigargin. These transcripts were enriched in GO categories related to cell division, miotic cell cycle, and microtubule‐based movement. Total of 60 transcripts (up = 41, down = 19) were only differentially expressed in cognitively normal older adults dermal fibroblast by ER stress‐thabsigargin. These transcripts were enriched in GO categories related to cholesterol biosynthesis process, DNA replication checkpoint, and cAMP‐mediated signaling. Conclusion: We identified transcriptional regulation landscape by ER stress‐thabsigargin in AD dementia and cognitively normal older adults dermal fibroblast. Further bioinformatic analysis with computational tools and validation experiments will be performed to find potential therapeutic targets against ER stress. [ABSTRACT FROM AUTHOR]

Background: Reactive oxygen species (ROS) is considered as a central pathophysiology for neurodegeneration in Alzheimer's disease (AD). Many studies using in vitro cell line or in vivo mouse model have shown the possible association between ROS defense mechanisms and cellular damage. However, that connection was not elucidated well in AD patient‐derived cell or brain organoids. In this study, we aimed to identify transcriptional regulation landscape and potential therapeutic targets against oxidative stress using AD dementia patient‐derived dermal fibroblast Methods: For the purposes of ex vivo research, we performed skin biopsy and stabilized dermal fibroblasts in vitro. Total of 20 AD dementia patients and 22 cognitively normal older adults were assessed. All of AD dementia patients were amyloid positive on PET imaging, APOE e4 carrier, and cognition was imparied. On the contrary, all of cognitively normal older adults were amyloid negative on PET imaging, and APOE e4 non‐carrier. We applied H2O2 (600 uM) to dermal fibroblast for 24 hours as an oxidant agent to promote oxidative stress. After that, to identify transcriptional regulation landscape against oxidative stress, RNA sequencing was performed. Results: Total of 406 transcripts (up = 61, down = 345) were commonly differentially expressed in both of AD dementia and cognitively normal older adults derived dermal fibroblast by ROS‐H2O2. These transcripts were enriched in GO categories related to cell division, cell cycle, and DNA repair. Interestingly, 133 transcripts (up = 41, down = 92) were only differentially expressed in AD dementia dermal fibroblast by ROS‐H2O2. These transcripts were enriched in GO categories related to DNA duplex unwinding, cell division, and DNA replication. Total of 147 transcripts (up = 67, down = 80) were only differentially expressed in cognitively normal older adults dermal fibroblast by ROS‐H2O2. These transcripts were enriched in GO categories related to negative regulation of cell proliferation, notch signaling pathway, and NMDA glutamate receptor signaling pathway. Conclusion: We identified transcriptional regulation landscape by ROS‐H2O2 in AD dementia and cognitively normal older adults dermal fibroblast. Further bioinformatic analysis with computational tools and validation experiments will be performed to find potential therapeutic targets against oxidative stress. [ABSTRACT FROM AUTHOR]

Background: The association between geriatric depressive symptoms and government‐initiated senior employment program (GSEP) according to the income level has not been thoroughly investigated. Identifying it may provide insights into executing senior employment programs and interventions. Method: Participants were 9287 adults, 65 or older, who participated in Living Profiles of Older People Survey (LPOPS) 2020. Korean version of the 15‐item Geriatric Depression Scale (SGDS‐K) was used to measure the main outcome, which was geriatric depressive symptoms and its three factors. The main exposure was employment status, GSEP, and the income level. A multiple linear regression analysis was performed. Result: Compared to being unemployed, being employed was associated with lower geriatric depressive symptoms regardless of income. In non‐GSEP jobs, higher income was proportionately associated with lower geriatric depressive symptoms but also higher life dissatisfaction. A group of GSEP jobs whose income level belonged to the first tertile (β of geriatric depressive symptoms = ‐1.027, β of life dissatisfaction = ‐0.510) was associated with lower geriatric depressive symptoms and life dissatisfaction compared to all tertiles of non‐GSEP jobs (β of geriatric depressive symptoms of first, second, and third tertile = ‐0.463, ‐0.542, ‐0.576; β of life dissatisfaction of first, second, and third tertile = ‐0.258, ‐0.176, ‐0.142). Conclusion: The group of GSEP jobs, whose income level belonged to the first tertile, was associated with lower geriatric depressive symptoms and lower life dissatisfaction compared to all tertiles of non‐GSEP jobs. We expect this result to give insights into implementing government policies and community‐based interventions. [ABSTRACT FROM AUTHOR]

Background: As the global elderly population increases, the prevalence of dementia is also increasing. Korea is one of the rapidly aging countries in the world, and 10.33% of elderly people aged 65 and older are receiving treatment for dementia as reported in 2021. Since disease modifying drugs have not yet been developed for dementia, the importance of modifiable risk factors that can lower the risk of dementia is being emphasized, and one of them is anemia in the elderly. We analyze national cohort data of approximately 20 years to disclose the relationship between anemia and dementia in Korean elderly, and suggest that anemia is a modifiable risk factor for dementia needed active intervention. Method: We analyzed a large population‐based cohort study of aged ³65 years who participated in the national health screening program including blood tests and cognitive function tests from 2007 to 2008 in Korean National Health Insurance Service database 2006‐2020. The risk of AD according to the presence and severity of anemia was evaluated using a multivariable Cox regression model, after adjustments for sex, BMI, HTN, DM, LDL, TG, SCr, GFR and past medical history (depression, HTN, DM, cardiovascular disease, cerebrovascular disease). Result: As a result of the analysis, dementia occurred in 27.9% of the total subjects (316,881 persons) during the follow‐up period until 2020. Also, dementia occurred in 27.5% of the normal group, but 30.1% of the anemia group. As a result of survival analysis, even after adjusting for sex, there was a statistically significant difference between the presence of anemia and the prevalence of dementia (HR 1.07, 95% CI 1.05‐1.09). In addition, even after adjusting for sex, BMI, HTN, DM, LDL, SCr, GFR, and past medical history, there was a statistically significant association between anemia and dementia (HR 1.05, 95% CI 1.03‐1.07). Conclusion: We reported that the presence of anemia statue and the severity of anemia in the elderly were related to the occurrence of dementia through a national date of Korea. We suggest that anemia is a modifiable risk factor for dementia and requires intensive intervention in the elderly. [ABSTRACT FROM AUTHOR]