Matthew J Y Kang, Dhamidhu Eratne, Samantha M Loi, Christa Dang, Alexander F Santillo, Henrik Zetterberg, Kaj Blennow, Philip B Mitchell, Malcolm Hopwood, Charles B Malpas, Dennis Velakoulis
{"title":"阿尔茨海默病的冷漠和情感性症状与血浆神经丝光升高有关，而与p-tau181无关。","authors":"Matthew J Y Kang, Dhamidhu Eratne, Samantha M Loi, Christa Dang, Alexander F Santillo, Henrik Zetterberg, Kaj Blennow, Philip B Mitchell, Malcolm Hopwood, Charles B Malpas, Dennis Velakoulis","doi":"10.1002/dad2.70151","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Apathy and affective neuropsychiatric symptoms (NPS) are prevalent in Alzheimer's disease (AD), yet their neurobiological cause is still unclear. We examined associations between plasma neurofilament light chain (NfL) and tau pathology (p-tau181) with apathy and affective symptoms in mild cognitive impairment (MCI) and AD dementia.</p><p><strong>Methods: </strong>This longitudinal study analyzed data from 781 participants with MCI and AD dementia enrolled in ADNI, with annual blood samples collected over 4 years. NPS were assessed via the Neuropsychiatric Interview (NPI), and biomarker trajectories were analyzed using mixed-effects models.</p><p><strong>Results: </strong>Elevated plasma NfL levels were associated with apathy, anxiety and depression in MCI and AD dementia, with apathy linked to a significantly higher rate of NfL increase, indicating accelerated neurodegeneration.</p><p><strong>Discussion: </strong>Apathy and affective symptoms may indicate greater neurodegenerative burden in AD independent of tau-related pathology. Apathy was associated with a steeper rise in plasma NfL, suggesting a more aggressive disease progression.</p><p><strong>Highlights: </strong>Apathy and affective neuropsychiatric symptoms (NPS) are highly prevalent in clinical Alzheimer's disease (AD).The presence of apathy, depression or anxiety was associated with higher plasma levels of neurofilament light chain (NfL).Apathy was associated with an accelerated increase in plasma NfL levels over time.Apathy and affective NPS were not associated with p-tau181 levels in plasma.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 3","pages":"e70151"},"PeriodicalIF":4.4000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305118/pdf/","citationCount":"0","resultStr":"{\"title\":\"Apathy and affective symptoms associated with elevated plasma neurofilament light but not p-tau181 in Alzheimer's disease.\",\"authors\":\"Matthew J Y Kang, Dhamidhu Eratne, Samantha M Loi, Christa Dang, Alexander F Santillo, Henrik Zetterberg, Kaj Blennow, Philip B Mitchell, Malcolm Hopwood, Charles B Malpas, Dennis Velakoulis\",\"doi\":\"10.1002/dad2.70151\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Apathy and affective neuropsychiatric symptoms (NPS) are prevalent in Alzheimer's disease (AD), yet their neurobiological cause is still unclear. We examined associations between plasma neurofilament light chain (NfL) and tau pathology (p-tau181) with apathy and affective symptoms in mild cognitive impairment (MCI) and AD dementia.</p><p><strong>Methods: </strong>This longitudinal study analyzed data from 781 participants with MCI and AD dementia enrolled in ADNI, with annual blood samples collected over 4 years. NPS were assessed via the Neuropsychiatric Interview (NPI), and biomarker trajectories were analyzed using mixed-effects models.</p><p><strong>Results: </strong>Elevated plasma NfL levels were associated with apathy, anxiety and depression in MCI and AD dementia, with apathy linked to a significantly higher rate of NfL increase, indicating accelerated neurodegeneration.</p><p><strong>Discussion: </strong>Apathy and affective symptoms may indicate greater neurodegenerative burden in AD independent of tau-related pathology. Apathy was associated with a steeper rise in plasma NfL, suggesting a more aggressive disease progression.</p><p><strong>Highlights: </strong>Apathy and affective neuropsychiatric symptoms (NPS) are highly prevalent in clinical Alzheimer's disease (AD).The presence of apathy, depression or anxiety was associated with higher plasma levels of neurofilament light chain (NfL).Apathy was associated with an accelerated increase in plasma NfL levels over time.Apathy and affective NPS were not associated with p-tau181 levels in plasma.</p>\",\"PeriodicalId\":53226,\"journal\":{\"name\":\"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring\",\"volume\":\"17 3\",\"pages\":\"e70151\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-07-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305118/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/dad2.70151\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/dad2.70151","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Apathy and affective symptoms associated with elevated plasma neurofilament light but not p-tau181 in Alzheimer's disease.
Introduction: Apathy and affective neuropsychiatric symptoms (NPS) are prevalent in Alzheimer's disease (AD), yet their neurobiological cause is still unclear. We examined associations between plasma neurofilament light chain (NfL) and tau pathology (p-tau181) with apathy and affective symptoms in mild cognitive impairment (MCI) and AD dementia.
Methods: This longitudinal study analyzed data from 781 participants with MCI and AD dementia enrolled in ADNI, with annual blood samples collected over 4 years. NPS were assessed via the Neuropsychiatric Interview (NPI), and biomarker trajectories were analyzed using mixed-effects models.
Results: Elevated plasma NfL levels were associated with apathy, anxiety and depression in MCI and AD dementia, with apathy linked to a significantly higher rate of NfL increase, indicating accelerated neurodegeneration.
Discussion: Apathy and affective symptoms may indicate greater neurodegenerative burden in AD independent of tau-related pathology. Apathy was associated with a steeper rise in plasma NfL, suggesting a more aggressive disease progression.
Highlights: Apathy and affective neuropsychiatric symptoms (NPS) are highly prevalent in clinical Alzheimer's disease (AD).The presence of apathy, depression or anxiety was associated with higher plasma levels of neurofilament light chain (NfL).Apathy was associated with an accelerated increase in plasma NfL levels over time.Apathy and affective NPS were not associated with p-tau181 levels in plasma.
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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