total tau or total tau and phosphorylated-tau 181 and Alzheimer's disease
Last edited 05/2022 and last reviewed 02/2023
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: