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Apathy and affective symptoms associated with elevated plasma neurofilament light but not p-tau181 in Alzheimer's disease

Kang, Matthew J.Y. ; Eratne, Dhamidhu ; Loi, Samantha M. ; Dang, Christa ; Santillo, Alexander F. LU orcid ; Zetterberg, Henrik LU ; Blennow, Kaj LU ; Mitchell, Philip B. ; Hopwood, Malcolm and Malpas, Charles B. , et al. (2025) In Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring 17(3).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, anxiety, apathy, blood-based biomarkers, depression, neurofilament light chain, neuropsychiatric symptoms, phosphorylated tau 181
in
Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
volume
17
issue
3
article number
e70151
publisher
Elsevier
external identifiers
  • scopus:105011951500
  • pmid:40735049
ISSN
2352-8729
DOI
10.1002/dad2.70151
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.
id
02a3fc35-3728-4e69-b2e1-ca2f7e9b2b54
date added to LUP
2025-08-04 17:51:58
date last changed
2025-08-06 03:01:38
@article{02a3fc35-3728-4e69-b2e1-ca2f7e9b2b54,
  abstract     = {{<p>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.</p>}},
  author       = {{Kang, Matthew J.Y. and Eratne, Dhamidhu and Loi, Samantha M. and Dang, Christa and Santillo, Alexander F. and Zetterberg, Henrik and Blennow, Kaj and Mitchell, Philip B. and Hopwood, Malcolm and Malpas, Charles B. and Velakoulis, Dennis}},
  issn         = {{2352-8729}},
  keywords     = {{Alzheimer's disease; anxiety; apathy; blood-based biomarkers; depression; neurofilament light chain; neuropsychiatric symptoms; phosphorylated tau 181}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{3}},
  publisher    = {{Elsevier}},
  series       = {{Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring}},
  title        = {{Apathy and affective symptoms associated with elevated plasma neurofilament light but not p-tau181 in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1002/dad2.70151}},
  doi          = {{10.1002/dad2.70151}},
  volume       = {{17}},
  year         = {{2025}},
}