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Subgroups of Alzheimer's disease based on cerebrospinal fluid molecular markers

Khalid Iqbal1, Michael Flory, Sabiha Khatoon

  • 1New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA. iqbalk@worldnet.att.net

Annals of Neurology
|October 26, 2005
PubMed

Insights

Alzheimer's disease may have distinct subgroups identifiable by cerebrospinal fluid (CSF) protein levels. Identifying these Alzheimer's disease subtypes could lead to personalized therapies targeting specific disease mechanisms.

Area of Science:

  • Neurology
  • Biochemistry
  • Medical Diagnostics

Background:

  • Alzheimer's disease (AD) is a complex, multifactorial dementia with probable diagnosis.
  • Current understanding suggests multiple underlying disease mechanisms contribute to AD pathology.
  • Identifying distinct AD subgroups could improve diagnosis and treatment.

Purpose of the Study:

  • To investigate if Alzheimer's disease can be subdivided based on cerebrospinal fluid (CSF) protein profiles.
  • To determine if these subgroups correlate with different clinical presentations.
  • To explore the potential for CSF biomarkers to guide targeted AD therapies.

Main Methods:

  • Immunoassays were used to measure tau, ubiquitin, and amyloid-beta (Abeta)(1-42) levels in CSF samples.
  • Retrospective analysis included 468 subjects: 353 with clinically diagnosed Alzheimer's disease and 115 controls.
  • Latent profile analysis was employed to cluster subjects based on molecular marker levels.

Main Results:

  • Alzheimer's disease was successfully subdivided into at least five distinct subgroups.
  • Subgroups were differentiated by CSF levels of Abeta(1-42), tau, and ubiquitin.
  • Each identified subgroup exhibited a unique clinical profile.

Conclusions:

  • Cerebrospinal fluid (CSF) analysis can identify distinct Alzheimer's disease subgroups.
  • These subgroups represent variations in underlying disease mechanisms.
  • Tailored therapeutic strategies may be more effective for specific Alzheimer's disease subtypes.

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