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Related Concept Videos

Alzheimer Disease l: Introduction01:29

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
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Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...

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Basics of Multivariate Analysis in Neuroimaging Data
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Multivariate models using NULISAseq and plasma p-tau217 for staging Alzheimer's disease.

James D Doecke1, Edwin Stage2, Christopher Fowler3

  • 1Australian E-Health Research Centre, CSIRO, Herston, Queensland, Australia.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
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Plasma phospho-tau217 (p-tau217) shows promise for Alzheimer

Keywords:
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Area of Science:

  • Neurodegenerative Diseases
  • Biomarker Discovery
  • Alzheimer's Disease Diagnostics

Background:

  • Plasma phospho-tau217 (p-tau217) demonstrates high performance in predicting amyloid beta (Aβ) positivity, comparable to cerebrospinal fluid (CSF) biomarkers.
  • While plasma p-tau217 offers confirmatory Aβ status information, optimal blood-based biomarkers (BBMs) for various Alzheimer's disease (AD) stages require further investigation.

Purpose of the Study:

  • To compare the predictive performance of individual p-tau217 assays against multi-biomarker panels for staging Alzheimer's disease (AD).
  • To evaluate the utility of additional blood-based biomarkers (BBMs) beyond p-tau217 for assessing AD progression.

Main Methods:

  • Utilized data from 387 participants in the Australian Imaging, Biomarkers and Lifestyle study.
  • Assessed participants using [18F]NAV4694 (Aβ) and [18F]MK-6240 (tau) PET scans.
  • Measured plasma p-tau217 using ALZpath and Lumipulse assays, and analyzed 370 proteins (CNS and inflammatory) via the Alamar Biosciences NULISASeq platform.

Main Results:

  • Multivariate blood-based biomarker (BBM) models significantly outperformed individual p-tau217 assays in predicting Alzheimer's disease (AD) stage.
  • The Lumipulse p-tau217 assay showed superior performance in differentiating disease stages compared to the ALZpath assay.
  • Multivariate BBM models demonstrated higher predictive accuracy (area under the curve) for disease staging than standalone p-tau217 assays, particularly in earlier stages.

Conclusions:

  • Combining p-tau217 with additional BBMs provides valuable insights into overall disease burden across different AD stages.
  • Multivariate BBM models offer enhanced predictive capability for AD diagnosis and staging compared to single biomarker approaches.
  • The Lumipulse assay is a more effective p-tau217 assay for distinguishing AD stages than the ALZpath assay.