Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

Yara Yakoub¹, Nicholas J Ashton^{2

3

4

5}, Cherie Strikwerda-Brown¹, Laia Montoliu-Gaya², Thomas K Karikari², Przemysław R Kac², Fernando Gonzalez-Ortiz², Jonathan Gallego-Rudolf¹, Pierre-François Meyer¹, Frédéric St-Onge¹, Michael Schöll^{2

3

6}, Jean-Paul Soucy⁷, John C S Breitner^{1

8

9}, Henrik Zetterberg^{2

6

10

11

12

13}, Kaj Blennow^{2

10}, Judes Poirier^{1

8}, Sylvia Villeneuve^{1

8}; PREVENT-AD Research Group

Affiliations

¹ Douglas Mental Health University Institute, Centre for Studies on the Prevention of Alzheimer's Disease (StoP-AD), Montreal, Quebec, Canada.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
⁴ King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.
⁵ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁶ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
⁷ Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
⁸ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁹ McGill Centre for Integrative Neuroscience, McGill University, Montreal, Quebec, Canada.
¹⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹¹ UK Dementia Research Institute at UCL, London, UK.
¹² Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
¹³ UW Department of Medicine, School of Medicine and Public Health, Madison, WI, USA.

PMID: 37294682
DOI: 10.1002/alz.13318

Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

Yara Yakoub et al. Alzheimers Dement. 2023 Dec.

. 2023 Dec;19(12):5620-5631.

doi: 10.1002/alz.13318. Epub 2023 Jun 9.

Authors

Affiliations

¹ Douglas Mental Health University Institute, Centre for Studies on the Prevention of Alzheimer's Disease (StoP-AD), Montreal, Quebec, Canada.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
⁴ King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.
⁵ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁶ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
⁷ Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
⁸ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁹ McGill Centre for Integrative Neuroscience, McGill University, Montreal, Quebec, Canada.
¹⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹¹ UK Dementia Research Institute at UCL, London, UK.
¹² Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
¹³ UW Department of Medicine, School of Medicine and Public Health, Madison, WI, USA.

PMID: 37294682
DOI: 10.1002/alz.13318

Abstract

Introduction: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset.

Methods: We measured longitudinal changes in plasma amyloid-beta (Aβ)_42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aβ and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers' progression.

Results: Aβ_42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aβ-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals.

Discussion: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD.

Highlights: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD. Apolipoprotein E ε4 carriers experience faster increase in plasma pTau181 over time than non-carriers. Female sex showed accelerated increase in plasma GFAP over time compared to males. Aβ_42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden.

Keywords: Alzheimer's disease; Aβ; PET; biomarker; pTau; plasma.

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References

REFERENCES

1. Jack CR, Bennett DA, Blennow K, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer's disease. Alzheimer's Dement: J Alzheimer's Association. 2018;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018
1. Hubbard BM, Fentonm GW, Anderson JM. A quantitative histological study of early clinical and preclinical Alzheimer's disease. Neuropathol Appl Neurobiol. 1990;16(2):111-121. doi: 10.1111/j.1365-2990.1990.tb00940.x
1. Price JL, Morris JC. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease. Ann Neurol. 1999;45(3):358-368.
1. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's Dement: J Alzheimer's Association. 2011;7(3):263-269. doi: 10.1016/j.jalz.2011.03.005
1. Hansson O, Edelmayer RM, Boxer AL, et al. The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease. Alzheimer's Dement. 2022. doi: 10.1002/alz.12756

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Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

Affiliations

Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

Authors

Affiliations

Abstract

References

REFERENCES

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LinkOut - more resources

Full Text Sources

Medical

Miscellaneous