3 Key Takeaways
Plain English Summary- 01Core Finding
To evaluate prognostic and monitoring utility, respectively, linear mixed-effect models tested whether baseline level and longitudinal change (2-5 years) in plasma pTau217 were associated with longitudinal changes (2-8 years) in daily functioning (Clinical Dementia Rating-Sum of Boxes [CDR-SB]), global cognition (Montreal Cognitive Assessment [MoCA]), and 5 domain-specific cognitive indices.
- 02Study Evidence
Tested in a clinical evidence review (n = 131) at the clinical practice stage.
- 03Practical Meaning
Benefits and risks vary by individual health history — discuss with a healthcare professional.
What This Means for You
Plasma pTau217 is a promising prognostic, risk-stratification, and monitoring biomarker (measurable biological signal) of clinical progression in LBD, underscoring its utility for clinical practice and trials in mixed pathology groups.
The Discovery
Although plasma phosphorylated tau-217 (pTau217) detects co-occurring Alzheimer disease (AD) neuropathologic change in Lewy body disease (LBD), relationships with long-term clinical outcomes remain unclear. Our aim was to evaluate plasma pTau217 as a prognostic, risk-stratification, and monitoring biomarker (measurable biological signal) of cognitive and functional decline in LBD. This prospective longitudinal study included Stanford AD Research Center participants enrolled from 2015 to 2023 with plasma pTau217 data and clinical diagnoses of LBD spectrum, AD spectrum, or healthy control (HC). To evaluate prognostic and monitoring utility, respectively, linear mixed-effect models tested whether baseline level and longitudinal change (2-5 years) in plasma pTau217 were associated with longitudinal changes (2-8 years) in daily functioning (Clinical Dementia Rating-Sum of Boxes [CDR-SB]), global cognition (Montreal Cognitive Assessment [MoCA]), and 5 domain-specific cognitive indices. For risk stratification, baseline plasma pTau217 status was defined using an amyloid PET-derived, LBD-specific cut-point to examine whether participants with abnormal levels demonstrated faster clinical progression in separate linear-mixed effects and survival models. A total of 501 participants (mean[SD] age = 71.1[8.5]; 51.5% female) were included across LBD ( n = 131), AD ( n = 133), and HC ( n = 237) groups. In LBD, higher baseline plasma pTau217 was associated with faster CDR-SB increase ( β = 0.30; 95% CI [0.14, 0.45]; p < 0.001), MoCA decline ( β = -0.35; 95% CI [-0.57, -0.13]; p = 0.002), and cognitive index decline (all p ≤ 0.028). Participants with abnormal baseline pTau217 had a 0.85 points/year faster CDR-SB increase (95% CI [0.56, 1.15]; p < 0.001), 0.87 points/year faster MoCA decline (95% CI [-1.38, -0.37]; p = 0.001), faster decline on cognitive indices (all p ≤ 0.018), and a three-fold higher risk of diagnostically progressing to mild cognitive impairment or dementia (HR = 3.41; 95% CI [1.60, 7.28]; p = 0.002) compared to participants with normal pTau217. Faster longitudinal pTau217 increase was associated with faster CDR-SB increase ( β = 0.24; 95% CI [0.10, 0.38]; p = 0.003).
How It Works, Simply
This neurology research focuses on amyloid · Tau protein · Blood biomarker (measurable biological signal). Researchers evaluated it using a clinical evidence review (n = 131) at the clinical practice stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
To evaluate prognostic and monitoring utility, respectively, linear mixed-effect models tested whether baseline level and longitudinal change (2-5 years) in plasma pTau217 were associated with longitudinal changes (2-8 years) in daily functioning (Clinical Dementia Rating-Sum of Boxes [CDR-SB]), global cognition (Montreal Cognitive Assessment [MoCA]), and 5 domain-specific cognitive indices.
- 02Study Evidence
Tested in a clinical evidence review (n = 131) at the clinical practice stage.
- 03Practical Meaning
Benefits and risks vary by individual health history — discuss with a healthcare professional.
Biological Mechanism & Study Design
Study Design & Cohort
Clinical evidence review
Clinical evidence review (n = 131) · Clinical Practice
Biological Pathway & Modality
Amyloid · Tau protein · Blood biomarker
Intervention: Plasma P-Tau217 as a Prognostic, Monitoring, and Risk-Stratification Biomarker of
Experimental Findings & Endpoints
Although plasma phosphorylated tau-217 (pTau217) detects co-occurring Alzheimer disease (AD) neuropathologic change in Lewy body disease (LBD), relationships with long-term clinical outcomes remain unclear.
Our aim was to evaluate plasma pTau217 as a prognostic, risk-stratification, and monitoring biomarker of cognitive and functional decline in LBD. This prospective longitudinal study included Stanford AD Research Center participants enrolled from 2015 to 2023 with plasma pTau217 data and clinical diagnoses of LBD spectrum, AD spectrum, or healthy control (HC).
To evaluate prognostic and monitoring utility, respectively, linear mixed-effect models tested whether baseline level and longitudinal change (2-5 years) in plasma pTau217 were associated with longitudinal changes (2-8 years) in daily functioning (Clinical Dementia Rating-Sum of Boxes [CDR-SB]), global cognition (Montreal Cognitive Assessment [MoCA]), and 5 domain-specific cognitive indices. For risk stratification, baseline plasma pTau217 status was defined using an amyloid PET-derived, LBD-specific cut-point to examine whether participants with abnormal levels demonstrated faster clinical progression in separate linear-mixed effects and survival models.
A total of 501 participants (mean[SD] age = 71.1[8.5]; 51.5% female) were included across LBD ( n = 131), AD ( n = 133), and HC ( n = 237) groups. In LBD, higher baseline plasma pTau217 was associated with faster CDR-SB increase ( β = 0.30; 95% CI [0.14, 0.45]; p < 0.001), MoCA decline ( β = -0.35; 95% CI [-0.57, -0.13]; p = 0.002), and cognitive index decline (all p ≤ 0.028).
Participants with abnormal baseline pTau217 had a 0.85 points/year faster CDR-SB increase (95% CI [0.56, 1.15]; p < 0.001), 0.87 points/year faster MoCA decline (95% CI [-1.38, -0.37]; p = 0.001), faster decline on cognitive indices (all p ≤ 0.018), and a three-fold higher risk of diagnostically progressing to mild cognitive impairment or dementia (HR = 3.41; 95% CI [1.60, 7.28]; p = 0.002) compared to participants with normal pTau217. Faster longitudinal pTau217 increase was associated with faster CDR-SB increase ( β = 0.24; 95% CI [0.10, 0.38]; p = 0.003).
Clinical Translation & Practice Context
Plasma pTau217 is a promising prognostic, risk-stratification, and monitoring biomarker of clinical progression in LBD, underscoring its utility for clinical practice and trials in mixed pathology groups.
The Bottom Line · Clinical Pearl
“Plasma pTau217 is a promising prognostic, risk-stratification, and monitoring biomarker of clinical progression in LBD, underscoring its utility for clinical practice and trials in mixed pathology groups. Although plasma phosphorylated tau-217 (pTau217) detects co-occurring Alzheimer disease (AD) neuropathologic change in Lewy body disease (LBD), relationships with long-term clinical outcomes remain unclear.”
Published in Neurology · Current Stage: Clinical Practice
