Plasma Leptin and Alzheimer Protein Pathologies Among Older Adults
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Published:2024-05-03
Issue:5
Volume:7
Page:e249539
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ISSN:2574-3805
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Container-title:JAMA Network Open
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language:en
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Short-container-title:JAMA Netw Open
Author:
Lee Seunghoon1, Byun Min Soo23, Yi Dahyun4, Ahn Hyejin5, Jung Gijung4, Jung Joon Hyung6, Chang Yoon Young7, Kim Kyungtae2, Choi Hyeji2, Choi Jeongmin2, Lee Jun-Young8, Kang Koung Mi9, Sohn Chul-Ho9, Lee Yun-Sang10, Kim Yu Kyeong11, Lee Dong Young2345, , Mook Inhee12, Choi Murim12, Lee Yu Jin12, Hahn Seokyung12, Kim Hyun Jung12, Chang Mun Young12, Han Na Young12, Pae Jisoo12, Park Hansoo12, Kim Jee Wook12, Lee Jong-Min12, Lee Dong Woo12, Sohn Bo Kyung12, Moon Seok Woo12, Baek Hyewon12, Kim Yoon-Keun12, Kim Jong-Won12, Ryu Seung-Ho12, Kim Shin Gyeom12, Woo Jong Inn12, Kim Sang Eun12, Cheon Gi Jeong12, Kang Koung Mi12, Park Jee-Eun12, Yu Hyeong Gon12, Choi Hyo Jung12, choe Young Min12, Kim Kwangsoo12, Jeon So Yeon12, Kim Woo Jin12, Ko Kang12, Lee Jun Ho12, Park Sung Wook12, Jung Gijung12, Joung Haejung12, Ann HyeJin12, Lee Han Na12, Jung Joon Hyung12, Byeon Gihwan12, Sung Kiyoung12, Han Dong Kyun12, Han Seung Min12, Kim Min Jung12, Kim Min Jae12, Kong Nayeong12, Park Seo Hee12, Kim Mimi12, Cha Woojin12, Yeom Hyeryeon12, Chang Yoon Young12, Keum Musung12, Kim Min Jeong12, Kim Donghee12, Kim Kyungtae12, Choi Jeongmin12, Choi Hye Ji12, Bae Han Sol12, Woo Dohyun12, Ha Seunghyuk12
Affiliation:
1. Department of Psychiatry, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea 2. Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea 3. Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea 4. Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea 5. Interdisciplinary Program of Cognitive Science, Seoul National University College of Humanities, Seoul, Republic of Korea 6. Department of Psychiatry, Chungbuk National University Hospital, Cheongju, Republic of Korea 7. Department of Psychiatry, Inje University, Sanggye Paik Hospital, Seoul, Republic of Korea 8. Department of Neuropsychiatry, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea 9. Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea 10. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea 11. Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea 12. for the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease (KBASE) Research Group
Abstract
ImportanceMany epidemiologic studies have suggested that low levels of plasma leptin, a major adipokine, are associated with increased risk of Alzheimer disease (AD) dementia and cognitive decline. Nevertheless, the mechanistic pathway linking plasma leptin and AD-related cognitive decline is not yet fully understood.ObjectiveTo examine the association of plasma leptin levels with in vivo AD pathologies, including amyloid-beta (Aβ) and tau deposition, through both cross-sectional and longitudinal approaches among cognitively unimpaired older adults.Design, Setting, and ParticipantsThis was a longitudinal cohort study from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer Disease. Data were collected from January 1, 2014, to December 31, 2020, and data were analyzed from July 11 to September 6, 2022. The study included a total of 208 cognitively unimpaired participants who underwent baseline positron emission tomography (PET) scans for brain Aβ deposition. For longitudinal analyses, 192 participants who completed both baseline and 2-year follow-up PET scans for brain Aβ deposition were included.ExposurePlasma leptin levels as assessed by enzyme-linked immunosorbent assay.Main Outcomes and MeasuresBaseline levels and longitudinal changes of global Aβ and AD-signature region tau deposition measured by PET scans.ResultsAmong the 208 participants, the mean (SD) age was 66.0 (11.3) years, 114 were women (54.8%), and 37 were apolipoprotein E ε4 carriers (17.8%). Lower plasma leptin levels had a significant cross-sectional association with greater brain Aβ deposition (β = −0.04; 95% CI, −0.09 to 0.00; P = .046), while there was no significant association between plasma leptin levels and tau deposition (β = −0.02; 95% CI, −0.05 to 0.02; P = .41). In contrast, longitudinal analyses revealed that there was a significant association between lower baseline leptin levels and greater increase of tau deposition over 2 years (β = −0.06; 95% CI, −0.11 to −0.01; P = .03), whereas plasma leptin levels did not have a significant association with longitudinal change of Aβ deposition (β = 0.006; 95% CI, 0.00-0.02; P = .27).Conclusions and RelevanceThe present findings suggest that plasma leptin may be protective for the development or progression of AD pathology, including both Aβ and tau deposition.
Publisher
American Medical Association (AMA)
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