Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Pratishtha Chatterjee^{1

2}, Steve Pedrini², Nicholas J Ashton^{3

4

5}, Michelle Tegg², Kathryn Goozee^{1

2

6

7

8}, Abhay K Singh⁹, Thomas K Karikari³, Joel Simrén^{3

10}, Eugeen Vanmechelen¹¹, Nicola J Armstrong¹², Eugene Hone², Prita R Asih^{13

14}, Kevin Taddei^{2

15}, Vincent Doré^{16

13}, Victor L Villemagne^{13

17}, Hamid R Sohrabi^{1

2

6

15

18}, Henrik Zetterberg^{3

10

19

20}, Colin L Masters²¹, Kaj Blennow^{3

10}, Ralph N Martins^{1

2

6

7

8

15}

Affiliations

¹ Department of Biomedical Sciences, Macquarie University, North Ryde, New South Wales, Australia.
² School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
³ Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴ Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁵ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁶ School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia.
⁷ The Cooperative Research Centre for Mental Health, Carlton South, Australia.
⁸ KaRa Institute of Neurological Disease, Macquarie Park, Australia.
⁹ Macquarie Business School, Macquarie University, North Ryde, New South Wales, Australia.
¹⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹¹ ADx NeuroSciences, Gent, Belgium.
¹² Department of Mathematics & Statistics, Curtin University, Bentley, Western Australia, Australia.
¹³ Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
¹⁴ College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
¹⁵ Australian Alzheimer's Research Foundation, Nedlands, Western Australia, Australia.
¹⁶ eHealth, CSIRO Health and Biosecurity, Herston, Queensland, Australia.
¹⁷ Department of Psychiatry, University of Pittsburgh, Pennsylvania, USA.
¹⁸ Centre for Healthy Ageing, Health Future Institute, Murdoch University, Murdoch, Western Australia, Australia.
¹⁹ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
²⁰ UK Dementia Research Institute at UCL, London, UK.
²¹ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.

PMID: 34494715
DOI: 10.1002/alz.12447

Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Pratishtha Chatterjee et al. Alzheimers Dement. 2022 Jun.

. 2022 Jun;18(6):1141-1154.

doi: 10.1002/alz.12447. Epub 2021 Sep 8.

Authors

Affiliations

¹ Department of Biomedical Sciences, Macquarie University, North Ryde, New South Wales, Australia.
² School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
³ Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁴ Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁵ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁶ School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia, Australia.
⁷ The Cooperative Research Centre for Mental Health, Carlton South, Australia.
⁸ KaRa Institute of Neurological Disease, Macquarie Park, Australia.
⁹ Macquarie Business School, Macquarie University, North Ryde, New South Wales, Australia.
¹⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹¹ ADx NeuroSciences, Gent, Belgium.
¹² Department of Mathematics & Statistics, Curtin University, Bentley, Western Australia, Australia.
¹³ Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia.
¹⁴ College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
¹⁵ Australian Alzheimer's Research Foundation, Nedlands, Western Australia, Australia.
¹⁶ eHealth, CSIRO Health and Biosecurity, Herston, Queensland, Australia.
¹⁷ Department of Psychiatry, University of Pittsburgh, Pennsylvania, USA.
¹⁸ Centre for Healthy Ageing, Health Future Institute, Murdoch University, Murdoch, Western Australia, Australia.
¹⁹ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
²⁰ UK Dementia Research Institute at UCL, London, UK.
²¹ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.

PMID: 34494715
DOI: 10.1002/alz.12447

Abstract

Introduction: This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD).

Methods: Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ-) or presence (Aβ+) of brain amyloidosis.

Results: Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ- CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ- CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ- CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume.

Discussion: These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.

Keywords: Alzheimer's disease; amyloid beta; blood biomarkers; brain amyloid beta; diagnosis; glial fibrillary acidic protein; longitudinal monitoring; neurofilament light; p-tau181; p-tau231; preclinical Alzheimer's disease; single molecule array; tau.

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References

REFERENCES

1. Greenblat C, World Health Organization. Dementia. 2020. https://www.who.int/news-room/fact-sheets/detail/dementia.
1. Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013;12:357-367.
1. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367:795-804.
1. Verberk IMW, Thijssen E, Koelewijn J, Mauroo K, Vanbrabant J, de Wilde A, et al. Combination of plasma amyloid beta(1-42/1-40) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology. Alzheimers Res Ther. 2020;12:118.
1. Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19:422-433.

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Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Affiliations

Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

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LinkOut - more resources

Full Text Sources

Medical

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