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Related Concept Videos

Blood Studies for Cardiovascular System I: Cardiac Biomarkers01:20

Blood Studies for Cardiovascular System I: Cardiac Biomarkers

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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.
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
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Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers01:19

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Cardiac biomarkers are critical in diagnosing, prognosing, and managing cardiovascular diseases. Routine measurement of specific biomarkers such as B-type natriuretic peptide (BNP), C-reactive protein (CRP), and homocysteine (Hcy) is common practice in clinical settings to evaluate heart function and predict cardiovascular events.
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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Pratishtha Chatterjee1,2,3, Pawel Kalinowski4, Anne M Roberts5

  • 1The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Low cerebrospinal fluid amyloid precursor protein (APP) levels are linked to Alzheimer's disease (AD) dementia, especially in individuals with phosphorylated tau (p-tau) pathology. This finding helps understand atypical AD biomarker profiles.

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Area of Science:

  • Neuroscience
  • Biomarkers
  • Alzheimer's Disease Pathophysiology

Background:

  • Biomarker integration (amyloid-β and phosphorylated tau) has improved Alzheimer's disease (AD) diagnosis.
  • Atypical biomarker profiles (e.g., amyloid-β positive/phosphorylated tau negative) occur in 15-20% of clinically diagnosed AD cases, posing diagnostic challenges.
  • Investigating alternative pathophysiological mechanisms for AD-like symptoms in these atypical cases is crucial.

Purpose of the Study:

  • To investigate the role of cerebrospinal fluid (CSF) amyloid precursor protein (APP) in clinically diagnosed AD patients.
  • To explore the relationship between CSF APP levels and different biomarker profiles (amyloid-β and phosphorylated tau status).
  • To understand the contribution of APP disruptions to AD progression and cognitive decline.

Main Methods:

  • Analysis of CSF APP concentrations in two independent cohorts: ADNI (N=384) and ADC (N=419).
  • Correlation analysis of APP levels with phosphorylated tau (p-tau181) and the Aβ42/Aβ40 ratio.
  • Assessment of associations between APP levels and other biomarkers (NfL) and cognitive/functional scores (MMSE, CDR-SB).

Main Results:

  • CSF APP was significantly lower in phosphorylated tau-negative (T-) individuals compared to phosphorylated tau-positive (T+) individuals across all diagnostic groups.
  • APP reductions were most pronounced in T- cases with clinical AD diagnoses.
  • Low APP levels, particularly when combined with elevated p-tau181, were associated with the highest prevalence of AD-like dementia and the most severe cognitive and functional impairments.

Conclusions:

  • Low APP levels or elevated p-tau181 are associated with a high prevalence of AD-like dementia, with the greatest risk observed when both markers are present.
  • These findings reveal a distinct biological profile for T- status in clinically diagnosed AD, highlighting potential for diagnostic refinement.
  • Disruptions in APP production and processing may contribute to AD progression, influencing neuronal plasticity and cognitive function.