¹⁸F‐AV‐1451 and CSF T‐tau and P‐tau as biomarkers in Alzheimer's disease

<jats:title>Abstract</jats:title><jats:p>To elucidate the relationship between cerebrospinal fluid (<jats:styled-content style="fixed-case">CSF</jats:styled-content>) total‐tau (T‐tau) and phosphorylated tau (P‐tau) with the tau <jats:styled-content style="fixed-case">PET</jats:styled-content> ligand <jats:sup>18</jats:sup>F‐<jats:styled-content style="fixed-case">AV</jats:styled-content>‐1451 in Alzheimer's disease (<jats:styled-content style="fixed-case">AD</jats:styled-content>), we examined 30 cognitively healthy elderly (15 with preclinical <jats:styled-content style="fixed-case">AD</jats:styled-content>), 14 prodromal <jats:styled-content style="fixed-case">AD</jats:styled-content>, and 39 <jats:styled-content style="fixed-case">AD</jats:styled-content> dementia patients. <jats:styled-content style="fixed-case">CSF</jats:styled-content> T‐tau and P‐tau were highly correlated (<jats:italic>R</jats:italic> = 0.92, <jats:italic>P</jats:italic> < 0.001), but they were only moderately associated with retention of <jats:sup>18</jats:sup>F‐<jats:styled-content style="fixed-case">AV</jats:styled-content>‐1451, and mainly in demented <jats:styled-content style="fixed-case">AD</jats:styled-content> patients. <jats:sup>18</jats:sup>F‐<jats:styled-content style="fixed-case">AV</jats:styled-content>‐1451, but not <jats:styled-content style="fixed-case">CSF</jats:styled-content> T‐tau or P‐tau, was strongly associated with atrophy and cognitive impairment. <jats:styled-content style="fixed-case">CSF</jats:styled-content> tau was increased in preclinical <jats:styled-content style="fixed-case">AD</jats:styled-content>, despite normal <jats:sup>18</jats:sup>F‐<jats:styled-content style="fixed-case">AV</jats:styled-content>‐1451 retention. However, not all dementia <jats:styled-content style="fixed-case">AD</jats:styled-content> patients exhibited increased <jats:styled-content style="fixed-case">CSF</jats:styled-content> tau, even though <jats:sup>18</jats:sup>F‐<jats:styled-content style="fixed-case">AV</jats:styled-content>‐1451 retention was always increased at this disease stage. We conclude that <jats:styled-content style="fixed-case">CSF</jats:styled-content> T‐tau and P‐tau mainly behave as biomarkers of “disease state”, since they appear to be increased in many cases of <jats:styled-content style="fixed-case">AD</jats:styled-content> at all disease stages, already before the emergence of tau aggregates. In contrast, <jats:sup>18</jats:sup>F‐<jats:styled-content style="fixed-case">AV</jats:styled-content>‐1451 is a biomarker of “disease stage”, since it is increased in clinical stages of the disease, and is associated with brain atrophy and cognitive decline.</jats:p>