JAMA Neurology: Plasma p-tau217 and tau PET can be used to predict AD

Longitudinal tau PET is often used to study the effects of drugs targeting more upstream events in AD, including whether such treatments can slow tau accumulation and spread, which may indicate a positive clinical effect in addition to targeting
.

However, to effectively use longitudinal tau PET as an outcome in clinical trials, enrichment for individuals likely to show tau accumulation and spread during the trial is key

statistical consensus

Antoine Leuzy describes the results of longitudinal changes in [ ¹⁸ F]RO948 tau PET over the clinical course of AD and determines which biomarker combinations show the strongest associations with longitudinal tau PET and the richness of the best optimized clinical trial
.

The findings were published in the journal JAMA Neurology

¹⁸ JAMA

This longitudinal cohort study consecutively recruited amyloid beta (Aβ)-negative cognitively unimpaired (CU) participants, Aβ-positive CU individuals, Aβ-positive individuals with mild cognitive impairment (MCI), and AD dementia the individual
.

Baseline plasma and cerebrospinal fluid were collected for Aβ42/Aβ40, tau threonine-217 (p-tau217), p-tau181 and neurofilament photophosphorylation, magnetic resonance imaging, amyloid PET and tau PET

Baseline tau PET normalized uptake value ratio (SUVR) and annual percent change in tau PET SUVR for regions of interest using a data-driven approach combining clustering and event-based modeling
.

Regression models were used to examine associations between individual biomarkers and longitudinal tau PET, and to determine which combinations best predicted longitudinal tau PET

Percent annual change in EBM-based region of interest and Tau PET normalized absorbance values ​​based on EBM stage

Percent annual change in EBM-based region of interest and Tau PET normalized absorbance values ​​based on EBM stage

Of the 343 participants, the mean (SD) age was 72.
56 (7.
24) years, and 157 (51.
1%) were female
.

The cluster/event-based modeling approach identified five regions (stages) of interest

Plasma p-tau217 (R2 = 0.
27, P < 0.
005), tau PET (Stage I baseline SUVR; R2 = 0.
13, P < 0.
05) and amyloid when looking at individual predictors and tau PET at stage showing the most variation PET (R2 = 0.
10, P < 0.
05) was significantly associated with stage I longitudinal tau PET in Aβ-positive CU individuals
.

Plasma p-tau217 (R2 = 0.
27, P < 0.
005), tau PET (Stage I baseline SUVR; R2 = 0.
13, P < 0.
05) and amyloid when looking at individual predictors and tau PET at stage showing the most variation PET (R2 = 0.
10, P < 0.
05) was significantly associated with stage I longitudinal tau PET in Aβ-positive CU individuals
.

In Aβ-positive individuals with MCI, plasma p-tau217 (R2 = 0.
24, P < 0.
005) and tau PET (stage II baseline SUVR; R2 = 0.
44, P < .
001) were significantly associated with stage II longitudinal tau PET
.

In Aβ-positive individuals with MCI, plasma p-tau217 (R2 = 0.
24, P < 0.
005) and tau PET (stage II baseline SUVR; R2 = 0.
44, P < .
001) were significantly associated with stage II longitudinal tau PET
.

For the efficacy analysis component, plasma p-tau217 and tau PET resulted in a 43% (95% CI, 34%-46%; P < 0.
005) reduction in the sample size of Aβ-positive CU individuals and a 68% (95%) reduction in Aβ-positive MCI individuals.
CI, 61%-73%; P < 0.
001)
.

Plasma p-tau217 and tau PET may be the best choice for preclinical and prodromal AD enrichment
.

However, plasma p-tau217 is most important in preclinical AD, and tau PET is more important in prodromal AD

Plasma p-tau217 and tau PET may be the best choice for preclinical and prodromal AD enrichment

Leuzy A, Smith R, Cullen NC, et al.

Leuzy A, Smith R, Cullen NC, et al.
Biomarker-Based Prediction of Longitudinal Tau Positron Emission Tomography in Alzheimer Disease.
  JAMA Neurol.
 Published online December 20, 2021.
doi:10.
1001/jamaneurol.
2021.
4654 Leuzy A, Smith R, Cullen NC, et al.
Biomarker-Based Prediction of Longitudinal Tau Positron Emission Tomography in Alzheimer Disease.
  JAMA Neurol.
 Published online December 20, 2021.
doi:10.
1001/jamaneurol.
2021.
4654 JAMA Neurol.
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