Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/34200
Title: Two-Year Prognostic Utility of Plasma p217+tau across the Alzheimer's Continuum.
Austin Authors: Feizpour, A;Doré, V;Doecke, J D;Saad, Z S;Triana-Baltzer, G;Slemmon, R;Maruff, P;Krishnadas, N;Bourgeat, P;Huang, K;Fowler, C;Rainey-Smith, S R;Bush, A I;Ward, L;Robertson, J;Martins, R N;Masters, C L;Villemagne, V L;Fripp, J;Kolb, H C;Rowe, Christopher C 
Affiliation: Molecular Imaging and Therapy
Issue Date: 2023
Publication information: The Journal of Prevention of Alzheimer's Disease 2023; 10(4)
Abstract: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid-β (Aβ) and tau in Alzheimer's Disease (AD). However, its association with longitudinal cognition and comparative performance to PET Aβ and tau in predicting cognitive decline are unknown. To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on Aβ (18F-NAV4694) and tau (18F-MK6240) PET. We also explored the sample size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost using p217+tau (pT+) as compared to PET Aβ (A+) and tau (T+) with and without p217+tau pre-screening. A prospective observational cohort study. Participants of the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and Australian Dementia Network (ADNeT). 153 cognitively unimpaired (CU) and 50 cognitively impaired (CI) individuals. Baseline p217+tau Simoa® assay, 18F-MK6240 tau-PET and 18F-NAV4694 Aβ-PET with neuropsychological follow-up (MMSE, CDR-SB, AIBL-PACC) over 2.4 ± 0.8 years. In CI, p217+tau was a significant predictor of change in MMSE (β = -0.55, p < 0.001) and CDR-SB (β =0.61, p < 0.001) with an effect size similar to Aβ Centiloid (MMSE β = -0.48, p = 0.002; CDR-SB β = 0.43, p = 0.004) and meta-temporal (MetaT) tau SUVR (MMSE: β = -0.62, p < 0.001; CDR-SB: β = 0.65, p < 0.001). In CU, only MetaT tau SUVR was significantly associated with change in AIBL-PACC (β = -0.22, p = 0.008). Screening pT+ CI participants into a trial could lead to 24% reduction in sample size compared to screening with PET for A+ and 6-13% compared to screening with PET for T+ (different regions). This would translate to an 81-83% biomarker test cost-saving assuming the p217+tau test cost one-fifth of a PET scan. In a trial requiring PET A+ or T+, p217+tau pre-screening followed by PET in those who were pT+ would cost more in the CI group, compared to 26-38% biomarker test cost-saving in the CU. Substantial cost reduction can be achieved using p217+tau alone to select participants with MCI or mild dementia for a clinical trial designed to slow cognitive decline over two years, compared to participant selection by PET. In pre-clinical AD trials, p217+tau provides significant cost-saving if used as a pre-screening measure for PET A+ or T+ but in MCI/mild dementia trials this may add to cost both in testing and in the increased number of participants needed for testing.
URI: https://ahro.austin.org.au/austinjspui/handle/1/34200
DOI: 10.14283/jpad.2023.83
ORCID: 
Journal: The Journal of Prevention of Alzheimer's Disease
Start page: 828
End page: 836
PubMed URL: 37874105
ISSN: 2426-0266
Type: Journal Article
Subjects: Alzheimer’s disease
Blood based biomarkers
clinical trials
cognition
pTau.
Alzheimer Disease/diagnostic imaging
Alzheimer Disease/cerebrospinal fluid
tau Proteins/cerebrospinal fluid
Amyloid beta-Peptides/cerebrospinal fluid
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