Cerebrospinal fluid

Dementia

CSF biomarkers for Alzheimer’s disease demonstrate characteristic low amyloid-β1-42 (Aβ42) and high total and phosphorylated tau (p-tau) levels. 166

When predicting if MCI would develop incipient AD: 166

• Aβ42 ≤482ng/L
  • Sensitivity: 79%
  • Specificity: 65%
  • Positive likelihood ratio: 2.3
  • Negative likelihood ratio: 0.32
• T-tau ≥320ng/L
  • Sensitivity: 86%
  • Specificity: 56%
  • Positive likelihood ratio: 1.9
  • Negative likelihood ratio: 0.26
• P-tau ≥52ng/L
  • Sensitivity: 84%
  • Specificity: 47%
  • Positive likelihood ratio: 1.6
  • Negative likelihood ratio: 0.34
• Index of Aβ42:P-tau ratio (y) and T-tau (x)
  • Sensitivity: 83%
  • Specificity: 72%
  • Positive likelihood ratio: 3.0
  • Negative likelihood ratio: 0.24

• As patients become older, the presence of brain amyloid becomes more common and less specific to Alzheimer disease. Thus, it makes sense to get as a helpful diagnostic tool in patients that are in their 50’s or 60’s, but less so in their 70’s and 80’s.
• CSF studies in EOAD is similar to late-onset AD 93
  • Tau/p-tau levels among phenotypic variants, particularly PCA, may be lower 93
• FTD has no validated biomarkers (though presence of AD pattern may help rule out FTD, as it would be an exclusion criteria for FTD) 95

Autoimmune encephalitis

Importance of CSF vs serum testing: 140

• most patients with autoimmune encephalitis have CSF antibodies and relevant antibodies might be found only in CSF
• the repertoire of antibodies in the CSF and serum can be different in the same patient, and generally the CSF antibodies are more determinant of the clinical picture
• concentration of CSF antibodies may correlate better with clinical course
• neuronal antibody testing using serum / cell-based assays can lead to false positives / negatives, which rarely happens in CSF testing