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Cardiac biomarkers are enzymes, proteins, and hormones released into the blood when cardiac cells are injured. They are powerful tools for triaging.
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Brain structure in the cingulate cortex and locus coeruleus in late life is associated with engagement in complex mental activities across the life span.

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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Heidi I L Jacobs1, Prokopis C Prokopiou1

  • 1Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Dysfunction in the locus coeruleus-norepinephrine (LC-NE) system is linked to tau buildup and cognitive decline in early Alzheimer's disease (AD). Maintaining LC function may help delay AD progression.

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Area of Science:

  • Neuroscience
  • Neurology
  • Biomarkers

Background:

  • The locus coeruleus-norepinephrine (LC-NE) system shows early tau accumulation in Alzheimer's disease (AD).
  • Previous studies linked CSF tau to NE turnover and AD progression.
  • This study investigates LC activity in preclinical AD stages.

Purpose of the Study:

  • To examine the link between locus coeruleus (LC) activity and tau pathology.
  • To investigate the association between LC activity and cognitive decline in preclinical AD.
  • To explore the role of LC-NE system dysfunction in early AD pathogenesis.

Main Methods:

  • Task-based fMRI (novelty and arousal tasks) was used to assess LC activity in two cohorts.
  • Tau-PET, amyloid-PET, 7T LC-imaging, and plasma biomarkers (GFAP, ptau217, NfL) were employed.
  • Linear regression and mixed-effects models analyzed associations between LC activity, tau, and cognitive decline.

Main Results:

  • Lower novelty-related LC activity correlated with increased medial temporal lobe tau and memory decline, mediated by entorhinal tau, especially with elevated amyloid.
  • Reduced arousal-related LC activity and cortical NE transporter connectivity were linked to higher ptau217 and GFAP.
  • Lower cortical NE transporter connectivity predicted faster cognitive decline in individuals with elevated GFAP and ptau217.

Conclusions:

  • LC-NE system dysfunction contributes to tau accumulation and cognitive impairment in early AD.
  • Astrocyte reactivity plays a role in facilitating tau's downstream effects.
  • Preserving LC function may be a strategy to delay Alzheimer's disease progression.