CSF biomarkers and plasma p-tau181 as predictors of longitudinal tau accumulation: Implications for clinical trial design

Alexis Moscoso^{1

2}, Thomas K Karikari^{1

3}, Michel J Grothe^{1

2

4}, Nicholas J Ashton^{1

2

5

6}, Juan Lantero-Rodriguez¹, Anniina Snellman^{1

7}, Henrik Zetterberg^{1

8

9

10

11}, Kaj Blennow^{1

8}, Michael Schöll^{1

2

9}

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
³ Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁴ Unidad de Trastornos del Movimiento, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
⁵ King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.
⁶ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁷ Turku PET Centre, University of Turku, Turku, Finland.
⁸ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁹ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
¹⁰ UK Dementia Research Institute at University College London, London, UK.
¹¹ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.

PMID: 35226405
DOI: 10.1002/alz.12570

Free article

CSF biomarkers and plasma p-tau181 as predictors of longitudinal tau accumulation: Implications for clinical trial design

Alexis Moscoso et al. Alzheimers Dement. 2022 Dec.

Free article

. 2022 Dec;18(12):2614-2626.

doi: 10.1002/alz.12570. Epub 2022 Feb 28.

Authors

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
³ Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁴ Unidad de Trastornos del Movimiento, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
⁵ King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.
⁶ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁷ Turku PET Centre, University of Turku, Turku, Finland.
⁸ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁹ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
¹⁰ UK Dementia Research Institute at University College London, London, UK.
¹¹ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.

PMID: 35226405
DOI: 10.1002/alz.12570

Abstract

Introduction: Clinical trials targeting tau in Alzheimer's disease (AD) need to recruit individuals at risk of tau accumulation. Here, we studied cerebrospinal fluid (CSF) biomarkers and plasma phosphorylated tau (p-tau)181 as predictors of tau accumulation on positron emission tomography (PET) to evaluate implications for trial designs.

Methods: We included older individuals who had serial tau-PET scans, baseline amyloid beta (Aβ)-PET, and baseline CSF biomarkers (n = 163) or plasma p-tau181 (n = 74). We studied fluid biomarker associations with tau accumulation and estimated trial sample sizes and screening failure reductions by implementing these markers into participant selection for trials.

Results: P-tau181 in CSF and plasma predicted tau accumulation (r > 0.36, P < .001), even in AD-continuum individuals with normal baseline tau-PET (A+T-; r > 0.37, P < .05). Recruitment based on CSF biomarkers yielded comparable sample sizes to Aβ-PET. Prescreening with plasma p-tau181 reduced up to ≈50% of screening failures.

Discussion: Clinical trials testing tau-targeting therapies may benefit from using fluid biomarkers to recruit individuals at risk of tau aggregation.

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References

REFERENCES

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CSF biomarkers and plasma p-tau181 as predictors of longitudinal tau accumulation: Implications for clinical trial design

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CSF biomarkers and plasma p-tau181 as predictors of longitudinal tau accumulation: Implications for clinical trial design

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