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Related Concept Videos

Alzheimer's Disease: Overview01:26

Alzheimer's Disease: Overview

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Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
451

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Defining Alzheimer's Disease through Proteomic CSF Profiling.

Carmen Peña-Bautista1, Lourdes Álvarez-Sánchez1, Ángel Balaguer2

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Alzheimer disease (AD) involves complex pathways. Proteomic analysis of cerebrospinal fluid revealed distinct protein profiles and identified two subtypes of mild cognitive impairment due to AD, highlighting disease heterogeneity.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Proteomics

Background:

  • Alzheimer disease (AD) is a leading cause of dementia with incompletely understood complexity.
  • Proteomic profiling offers insights into AD pathways and patient heterogeneity.

Purpose of the Study:

  • To investigate proteomic profiles in cerebrospinal fluid (CSF) from individuals with mild cognitive impairment due to AD (MCI-AD) and controls.
  • To identify proteins and biological processes associated with MCI-AD and AD biomarkers.

Main Methods:

  • Proteomic analysis of CSF samples from MCI-AD and control groups.
  • Classification of participants based on CSF amyloid β42/amyloid β40 levels.
  • Analysis using Partial Least Squares (PLS) regression and volcano plots.

Main Results:

  • Identified 7 key proteins (FOLR2, PPP3CA, SMOC2, STMN1, TAGLN3, TMEM132B, UCHL1) linked to phosphorylation, structure, inflammation, and degradation.
  • Enrichment analysis indicated involvement of neuronal, synaptic, metabolic, immune, vascular, and signaling pathways.
  • Discovered two MCI-AD subgroups: one associated with synaptic/neuronal functions, the other with innate immunity.
  • Proteomic profiles showed associations with CSF AD biomarker levels.

Conclusions:

  • CSF proteomic profiles reflect the biochemical heterogeneity of Alzheimer disease.
  • Distinct MCI-AD subgroups suggest different underlying pathological mechanisms, potentially impacting therapeutic strategies.