Comparison of Plasma Phosphorylated Tau Species With Amyloid and Tau Positron Emission Tomography, Neurodegeneration, Vascular Pathology, and Cognitive Outcomes

Mielke, Michelle M.; Frank, Ryan D.; Dage, Jeffrey L.; Jeromin, Andreas; Ashton, Nicholas J.; Blennow, Kaj; Karikari, Thomas K.; Vanmechelen, Eugeen; Zetterberg, Henrik; Algeciras‐Schimnich, Alicia; Knopman, David S.; Lowe, Val J.; Bu, Guojun; Vemuri, Prashanthi; Graff‐Radford, Jonathan; Jack, Clifford R.; Petersen, Ronald C.

doi:10.1001/jamaneurol.2021.2293

Cited by 149 publications

(216 citation statements)

References 43 publications

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“…The three P-tau181 assays and P-tau217 Eli Lilly and P-tau231 Gothenburg assays performed excellent in discriminating between controls and patients with AD dementia, with AUCs > 0.93, while the prototype P-tau231 ADx assay performed moderately with AUC = 0.72. The high AUCs observed for discriminating patients with AD dementia and controls with plasma P-tau181, P-tau217 Eli Lilly, and P-tau231 Gothenburg assays are in line with several previous reports in large cohorts using the same reagents but employing the MSD platform [ 4 , 8 , 16 , 18 , 26 – 28 ]. Likewise, the high AUC obtained with the P-tau181 Quanterix assay is in line with recent publications using a homebrew assay that employs the same antibodies as the Quanterix assay [ 5 , 9 ].…”

Section: Discussionsupporting

confidence: 90%

Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231

et al. 2021

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Introduction Studies using different assays and technologies showed highly promising diagnostic value of plasma phosphorylated (P-)tau levels for Alzheimer’s disease (AD). We aimed to compare six P-tau Simoa assays, including three P-tau181 (Eli Lilly, ADx, Quanterix), one P-tau217 (Eli Lilly), and two P-tau231 (ADx, Gothenburg). Methods We studied the analytical (sensitivity, precision, parallelism, dilution linearity, and recovery) and clinical (40 AD dementia patients, age 66±8years, 50%F; 40 age- and sex-matched controls) performance of the assays. Results All assays showed robust analytical performance, and particularly P-tau217 Eli Lilly; P-tau231 Gothenburg and all P-tau181 assays showed robust clinical performance to differentiate AD from controls, with AUCs 0.936–0.995 (P-tau231 ADx: AUC = 0.719). Results obtained with all P-tau181 assays, P-tau217 Eli Lilly assay, and P-tau231 Gothenburg assay strongly correlated (Spearman’s rho > 0.86), while correlations with P-tau231 ADx results were moderate (rho < 0.65). Discussion P-tau isoforms can be measured robustly by several novel high-sensitive Simoa assays.

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Section: Discussionsupporting

confidence: 90%

Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231

et al. 2021

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“…The present work confirms that therapeutic gardening can be helpful not only in "pure" forms of Alzheimer's disease (only a small number of the studies reviewed considered this type of patient), but also in the more common mixed forms of dementia [70,71].…”

Section: Research Questions and Related Answerssupporting

confidence: 82%

Effectiveness of Therapeutic Gardens for People with Dementia: A Systematic Review

Murroni

Cavalli

Basso³

et al. 2021

IJERPH

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This paper is a systematic review of quantitative studies conducted on the benefits of visiting gardens and gardening therapy for people with dementia (PWD) in an effort to assess the effectiveness of such treatments and obtain information on the most appropriate garden design for this population. This review followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) guidelines. Four databases were searched (PubMed, Web of Science, PsycINFO, Scopus), with no time limits. Out of a total of 480 articles considered, 16 studies were selected for review. In all but two of the studies examined, gardening therapy and the use of therapeutic gardens induced psychophysiological improvements in PWD. The areas showing the greatest effects were Engagement, Agitation, Depression/Mood, Stress, and Medication. It also emerged that interest in this sphere has been growing in the last decade, but there is still a shortage of empirical evidence of the beneficial effects of therapeutic gardens in relation to the type and severity of dementia, and of garden design guidelines. Despite the limited number of studies investigated, the review confirmed the benefits of gardening and therapeutic gardens in PWD. There is nonetheless a need to conduct more quantitative research to support currently-available evidence and generate more information, focusing on garden design criteria, in-garden activities, the type and severity of dementia examined, and effects on caregivers as well as on PWD.

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“…P-tau181 was also a good predictor of elevated brain Aβ and tau as measured by PET [7]. Subsequently, plasma P-tau217 and P-tau231 have also shown strong association with AD pathology with accuracy comparable to CSF and PET measures [8, 9] with some evidence of superior performance to plasma P-tau181 [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Plasma p217+tau vs NAV4694 amyloid and MK6240 tau PET across the Alzheimer continuum

Doré

Doecke

Saad

et al. 2022

Preprint

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INTRODUCTION: We evaluated a new Simoa plasma assay for phosphorylated tau at aa217 enhanced by additional ptau sites (p217+tau). METHODS: Plasma p217+tau levels were compared to 18F-NAV4694 amyloid-beta (Aβ PET and 18F-MK6240 tau PET in 174 cognitively impaired (CI) and 223 cognitively unimpaired (CU) participants. RESULTS: Compared to Aβ- CU, the plasma levels of p217+tau increased two-fold in Aβ+ CU and 3.5-fold in Aβ+ CI. In Aβ- the p217+tau levels did not significantly differ between CU, MCI or dementia. P217+tau correlated with Aβ centiloids ρ=0.67 (CI 0.64; CU 0.45) and tau SUVRMT ρ=0.63 (CI 0.69; CU 0.34). Area under curve (AUC) for AD vs Aβ- CU was 0.94, for AD vs other dementia was 0.93, for Aβ+ vs Aβ PET was 0.89 and for tau+ vs tau- PET was 0.89. DISCUSSION: Plasma p217+tau levels elevate early in the AD continuum and correlate well with Aβ and tau PET.

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Comparison of Plasma Phosphorylated Tau Species With Amyloid and Tau Positron Emission Tomography, Neurodegeneration, Vascular Pathology, and Cognitive Outcomes

Cited by 149 publications

References 43 publications

Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231

Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231

Effectiveness of Therapeutic Gardens for People with Dementia: A Systematic Review

Plasma p217+tau vs NAV4694 amyloid and MK6240 tau PET across the Alzheimer continuum

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