Gihwan Byeon, Suhyung Kim, Sunghwan Kim, Yoo Hyun Um, Sheng-Min Wang, Seunggyun Ha, Sonya Youngju Park, Yeong Sim Choe, Donghyeon Kim, Hyun Kook Lim, Chang Uk Lee, Dong Woo Kang
{"title":"可溶性淀粉样蛋白和斑块淀粉样蛋白对老年抑郁症的不同影响：tau病理的调节作用。","authors":"Gihwan Byeon, Suhyung Kim, Sunghwan Kim, Yoo Hyun Um, Sheng-Min Wang, Seunggyun Ha, Sonya Youngju Park, Yeong Sim Choe, Donghyeon Kim, Hyun Kook Lim, Chang Uk Lee, Dong Woo Kang","doi":"10.1016/j.tjpad.2025.100318","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Late-life depression frequently co-occurs with Alzheimer's disease (AD); however, the interactive effects of amyloid-beta (Aβ) species and tau pathology on depressive symptoms remain unclear. Soluble oligomeric Aβ (OAβ) and amyloid plaques may differentially influence depression depending on tau burden.</p><p><strong>Objectives: </strong>To examine how plasma OAβ and PET-measured amyloid plaque burden are associated with depressive symptoms across varying levels of tau pathology.</p><p><strong>Design: </strong>Cross-sectional analysis using generalized linear models with interaction terms, supported by stratified subgroup analyses and Johnson-Neyman procedures.</p><p><strong>Setting: </strong>Memory disorder clinic at a university-affiliated hospital.</p><p><strong>Participants: </strong>A total of 103 individuals, including cognitively normal controls (n = 24), patients with mild cognitive impairment (n = 54), and amyloid-positive dementia (n = 25), all of whom underwent plasma biomarker testing and tau and amyloid PET imaging.</p><p><strong>Measurements: </strong>Depression was evaluated using the Cornell Scale for Depression in Dementia (CSDD), Hamilton Depression Rating Scale (HAM-D), and Geriatric Depression Scale-Short Version (GDS-SV). Plasma OAβ was measured by Multimer Detection System (MDS), and PET quantified amyloid and tau burden.</p><p><strong>Results: </strong>MDS-OAβ showed a significant negative interaction with tau PET SUVR on depression scores (FDR-adjusted p < 0.05). Higher OAβ levels were linked to greater depression severity in low-tau individuals, but inversely related in high-tau individuals. Amyloid plaque burden was associated with depression only in those with advanced tau pathology.</p><p><strong>Conclusions: </strong>The association between amyloid pathology and depression differs depending on tau burden. Soluble OAβ may be a key contributor to depressive symptoms in early AD stages, while plaque effects become prominent later. These findings underscore the potential utility of OAβ as an early neuropsychiatric biomarker in AD and highlight the need to consider tau pathology when evaluating amyloid-related mood disturbances.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100318"},"PeriodicalIF":7.8000,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501351/pdf/","citationCount":"0","resultStr":"{\"title\":\"Differential effects of soluble and plaque amyloid on late-life depression: The moderating role of tau pathology.\",\"authors\":\"Gihwan Byeon, Suhyung Kim, Sunghwan Kim, Yoo Hyun Um, Sheng-Min Wang, Seunggyun Ha, Sonya Youngju Park, Yeong Sim Choe, Donghyeon Kim, Hyun Kook Lim, Chang Uk Lee, Dong Woo Kang\",\"doi\":\"10.1016/j.tjpad.2025.100318\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Late-life depression frequently co-occurs with Alzheimer's disease (AD); however, the interactive effects of amyloid-beta (Aβ) species and tau pathology on depressive symptoms remain unclear. Soluble oligomeric Aβ (OAβ) and amyloid plaques may differentially influence depression depending on tau burden.</p><p><strong>Objectives: </strong>To examine how plasma OAβ and PET-measured amyloid plaque burden are associated with depressive symptoms across varying levels of tau pathology.</p><p><strong>Design: </strong>Cross-sectional analysis using generalized linear models with interaction terms, supported by stratified subgroup analyses and Johnson-Neyman procedures.</p><p><strong>Setting: </strong>Memory disorder clinic at a university-affiliated hospital.</p><p><strong>Participants: </strong>A total of 103 individuals, including cognitively normal controls (n = 24), patients with mild cognitive impairment (n = 54), and amyloid-positive dementia (n = 25), all of whom underwent plasma biomarker testing and tau and amyloid PET imaging.</p><p><strong>Measurements: </strong>Depression was evaluated using the Cornell Scale for Depression in Dementia (CSDD), Hamilton Depression Rating Scale (HAM-D), and Geriatric Depression Scale-Short Version (GDS-SV). Plasma OAβ was measured by Multimer Detection System (MDS), and PET quantified amyloid and tau burden.</p><p><strong>Results: </strong>MDS-OAβ showed a significant negative interaction with tau PET SUVR on depression scores (FDR-adjusted p < 0.05). Higher OAβ levels were linked to greater depression severity in low-tau individuals, but inversely related in high-tau individuals. Amyloid plaque burden was associated with depression only in those with advanced tau pathology.</p><p><strong>Conclusions: </strong>The association between amyloid pathology and depression differs depending on tau burden. Soluble OAβ may be a key contributor to depressive symptoms in early AD stages, while plaque effects become prominent later. These findings underscore the potential utility of OAβ as an early neuropsychiatric biomarker in AD and highlight the need to consider tau pathology when evaluating amyloid-related mood disturbances.</p>\",\"PeriodicalId\":22711,\"journal\":{\"name\":\"The Journal of Prevention of Alzheimer's Disease\",\"volume\":\" \",\"pages\":\"100318\"},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2025-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501351/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Prevention of Alzheimer's Disease\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.tjpad.2025.100318\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BUSINESS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Prevention of Alzheimer's Disease","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.tjpad.2025.100318","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/5 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BUSINESS","Score":null,"Total":0}
Differential effects of soluble and plaque amyloid on late-life depression: The moderating role of tau pathology.
Background: Late-life depression frequently co-occurs with Alzheimer's disease (AD); however, the interactive effects of amyloid-beta (Aβ) species and tau pathology on depressive symptoms remain unclear. Soluble oligomeric Aβ (OAβ) and amyloid plaques may differentially influence depression depending on tau burden.
Objectives: To examine how plasma OAβ and PET-measured amyloid plaque burden are associated with depressive symptoms across varying levels of tau pathology.
Design: Cross-sectional analysis using generalized linear models with interaction terms, supported by stratified subgroup analyses and Johnson-Neyman procedures.
Setting: Memory disorder clinic at a university-affiliated hospital.
Participants: A total of 103 individuals, including cognitively normal controls (n = 24), patients with mild cognitive impairment (n = 54), and amyloid-positive dementia (n = 25), all of whom underwent plasma biomarker testing and tau and amyloid PET imaging.
Measurements: Depression was evaluated using the Cornell Scale for Depression in Dementia (CSDD), Hamilton Depression Rating Scale (HAM-D), and Geriatric Depression Scale-Short Version (GDS-SV). Plasma OAβ was measured by Multimer Detection System (MDS), and PET quantified amyloid and tau burden.
Results: MDS-OAβ showed a significant negative interaction with tau PET SUVR on depression scores (FDR-adjusted p < 0.05). Higher OAβ levels were linked to greater depression severity in low-tau individuals, but inversely related in high-tau individuals. Amyloid plaque burden was associated with depression only in those with advanced tau pathology.
Conclusions: The association between amyloid pathology and depression differs depending on tau burden. Soluble OAβ may be a key contributor to depressive symptoms in early AD stages, while plaque effects become prominent later. These findings underscore the potential utility of OAβ as an early neuropsychiatric biomarker in AD and highlight the need to consider tau pathology when evaluating amyloid-related mood disturbances.
期刊介绍：
The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
