Aims

We assessed the utility of plasma phosphorylated tau (P-tau) 181 and 217 as biomarkers of AD pathophysiology in a population-based setting and examined interclass correlation coefficients (ICC) to determine intra-individual variability over serial samples.

Methods

We included 1,329 Mayo Clinic Study on Aging participants (1,161 cognitively unimpaired, 153 MCI, 15 dementia), median age of 69 (range 30-98); 1,066 had amyloid PET and 495 tau PET. P-tau 181 and 217 was measured on the MSD platform; previous cutpoints were used for analyses. Elevated amyloid (A+) was defined as SUVR≥1.48 using PiB PET; elevated tau (T+) as SUVR≥1.25 using F-18-AV-1451. Area under the Receiver Operating Curve (AUROC) and diagnostic statistics were used to assess the accuracy of plasma P-tau for amyloid and tau PET. ICCs of P-tau levels were calculated.

Results

Among all participants, plasma P-tau181 predicted A+ with an AUROC of 0.71, 51% sensitivity, 92% specificity, and 81% positive predictive value (PPV). For P-tau217 and A+, the AUROC was 0.74, 51% sensitivity, 96% specificity, 90% PPV. Plasma P-tau181 predicted T+ with an AUROC of 0.59, 22% sensitivity, 95% specificity, 54% PPV. For P-tau 217, the AUROC was 0.63, 34% sensitivity, 92% specificity, 53% PPV. Both P-tau181 and 217 levels increased with clinical severity (CU<MCI<dementia, p<0.001). The ICC (95% CI) for Ptau181 was 0.92 (0.92, 0.93) and for Ptau217 was 0.95 (0.95, 0.96).

Conclusions

In this population-based sample, both plasma P-tau181 and 217 had good discrimination for A+, but discrimination for T+ was lower. There was low intra-individual variability over serial samples.

Abstract Body

Aims: In 2018 a workgroup commissioned by the National Institute on Aging and Alzheimer’s Association (NIA-AA) published a research framework in which Alzheimer’s disease (AD) is defined by the underlying pathologic processes rather than by the presence of an etiologically non-specific syndrome or syndromes. This shifts the definition of AD from a syndromal to a biological construct.

Methods: The research framework addresses both diagnosis (definition) and staging of AD. Biomarker and cognitive staging are performed independently from each other. AD can be documented by post-mortem examination or in vivo by biomarkers. Biomarkers are grouped into those of β-amyloid deposition, pathologic tau, and neurodegeneration (AT(N). Both imaging and biofluid (CSF and plasma) biomarkers exist within each AT(N) group.

Results: Since publication of the research framework, significant advances have occurred in development of plasma AT(N) biomarkers. As a results widespread application of a biological definition of AD and AT(N) biomarker phenotyping now seem possible. This has significant implications for design of clinical trials, observational research and clinical care.

Conclusions: Many unanswered questions exist concerning the appropriate roles and the interplay between traditional expensive or invasive AD biomarkers (CSF and imaging) and newer plasma biomarkers.

Abstract Body

Aims: In 2018 a workgroup commissioned by the National Institute on Aging and Alzheimer’s Association (NIA-AA) published a research framework in which Alzheimer’s disease (AD) is defined by the underlying pathologic processes rather than by the presence of an etiologically non-specific syndrome or syndromes. This shifts the definition of AD from a syndromal to a biological construct.

Methods: The research framework addresses both diagnosis (definition) and staging of AD. Biomarker and cognitive staging are performed independently from each other. AD can be documented by post-mortem examination or in vivo by biomarkers. Biomarkers are grouped into those of β-amyloid deposition, pathologic tau, and neurodegeneration (AT(N). Both imaging and biofluid (CSF and plasma) biomarkers exist within each AT(N) group.

Results: Since publication of the research framework, significant advances have occurred in development of plasma AT(N) biomarkers. As a results widespread application of a biological definition of AD and AT(N) biomarker phenotyping now seem possible. This has significant implications for design of clinical trials, observational research and clinical care.

Conclusions: Many unanswered questions exist concerning the appropriate roles and the interplay between traditional expensive or invasive AD biomarkers (CSF and imaging) and newer plasma biomarkers.