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Total tau or total tau and phosphorylated-tau 181 and Alzheimer's disease

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Three core CSF biomarkers for Alzheimer's disease have been developed, each correlating to one of the key characteristics of Alzheimer's disease pathology (1):

  • low levels of CSF amyloid-beta1-42 correlate with greater plaque load
  • high levels of total tau correlate with greater intensity of neuronal degeneration
  • high levels of phosphorylated tau correlate with neurofibrillary tangle pathology.

In the context of a clinical presentation consistent with Alzheimer's disease

  • presence of low levels of amyloid-beta1-42 in combination with high levels of total tau and phosphorylated tau provide support for the diagnosis with a sensitivity of 80-93% and specificity of 82-90% against cognitively normal controls (1)
    • other common dementia disorders can overlap with Alzheimer's disease both in terms of symptoms and CSF profile, and mixed pathologies are common.

A study by Skillback et al found (1):

  • frontotemporal dementia
    • highest cerebrospinal fluid levels of amyloid-beta1-42 and the lowest levels of total tau and phosphorylated tau
  • Alzheimer's disease
    • highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-beta1-42 and amyloid-beta1-42:phosphorylated tau ratios were found
    • low amyloid-beta1-42, high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease
  • in Parkinson's disease dementia and vascular dementia
    • low cerebrospinal fluid amyloid-beta1-42 was associated with low Mini-Mental State Examination score
  • cerebrospinal fluid biomarkers were strongly associated with specific clinical dementia diagnoses with Alzheimer's disease and frontotemporal dementia showing the greatest difference in biomarker levels
  • cerebrospinal fluid amyloid-beta1-42, total tau, phosphorylated tau and the amyloid-beta1-42:phosphorylated tau ratio all correlated with poor cognitive performance in Alzheimer's disease, as did cerebrospinal fluid amyloid-beta1-42 in Parkinson's disease dementia and vascular dementia.

NICE states (2):

  • further tests for Alzheimer's disease
    • if the diagnosis is uncertain and Alzheimer's disease is suspected, consider either:
      • FDG-PET (fluorodeoxyglucose-positron emission tomography-CT), or perfusion SPECT (single-photon emission CT) if FDG-PET is unavailable or
      • examining cerebrospinal fluid for:
        • either total tau or total tau and phosphorylated-tau 181 AND
        • either amyloid beta 1-42 or amyloid beta 1-42 and amyloid beta 1-40.

Reference:


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