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

Abstract

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

Cross‐sectional and longitudinal atrophy is preferentially associated with tau rather than amyloid β positron emission tomography pathology

“…This is consistent with prior work in the field demonstrating structural declines in preclinical AD [4,5,[8][9][10]. Early work has also indicated a significant relationship between tau PET binding and gray matter health [34][35][36][37]. When simultaneously considering both biomarkers, levels of tau PET mediated the effects of Ab on cortical thickness.…”

“…Alternatively, the temporal ordering of tau relative to structural MRI has been based on CSF total tau and phosphorylated tau. Although CSF and PET measures of tau are modestly correlated [23,29,37], these two markers likely measure distinct but related aspects of tau. Just as there appears to be a temporal lag between CSF and PET measures of Ab [49,50], there is likely a temporal delay between changes in CSF and PET measures of tau.…”

Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease

“…Plasma NfL and T‐tau were barely significant in the models ( P = 0.02 and P = 0.04, respectively; ). Since these latter two biomarkers are known to increase more markedly later in the disease (Mattsson et al , ,b, ,b), this finding can probably to some extent be explained by the fact that we only included non‐demented individuals. In contrast to the above plasma biomarkers, plasma P‐tau had a trajectory that was more alike the corresponding CSF biomarker (Fig B) and also had the highest r 2 value of all plasma biomarkers (), which in the present study highlights it as the best plasma biomarker to track Aβ accumulation.…”

Distinct tau PET patterns in atrophy‐defined subtypes of Alzheimer's disease

“…PET images were acquired using a Biograph mCT PET/ computed tomography scanner (Siemens Medical Solutions) in Seoul, Discovery 690 PET scanner (GE medical systems) in BioFINDER, a Biograph 6 Truepoint PET/ computed tomography scanner (Siemens Medical Solutions) at Lawrence Berkeley National Laboratory for UCSF patients, after a bolus injection of ∼370 MBq (BioFINDER and UCSF) or ∼280 MBq (Seoul) of [ 18 F]flortaucipir. PET data were locally reconstructed into 4 × 5‐minute frames for the 80‐ to 100‐min interval after injection . MRI scans were acquired at 3T on a Discovery MR750 scanner (GE medical systems) in Seoul, 3.0T Tim Trio or Skyra scanner (Siemens Medical Solutions) in BioFINDER, and a 3.0T Tim Trio or Prisma scanner (Siemens Medical Solutions) at UCSF.…”