Head-to-head comparison of plasma p-tau181, p-tau231 and glial fibrillary acidic protein in clinically unimpaired elderly with three levels of APOE4-related risk for Alzheimer's disease

Anniina Snellman; Laura L. Ekblad; Nicholas J. Ashton; Thomas K. Karikari; Juan Lantero-Rodriguez; Elina Pietilä; Mikko Koivumäki; Semi Helin; Mira Karrasch; Henrik Zetterberg; Kaj Blennow; Juha O. Rinne

Neurobiology of Disease (Jul 2023)

Head-to-head comparison of plasma p-tau181, p-tau231 and glial fibrillary acidic protein in clinically unimpaired elderly with three levels of APOE4-related risk for Alzheimer's disease

Anniina Snellman,
Laura L. Ekblad,
Nicholas J. Ashton,
Thomas K. Karikari,
Juan Lantero-Rodriguez,
Elina Pietilä,
Mikko Koivumäki,
Semi Helin,
Mira Karrasch,
Henrik Zetterberg,
Kaj Blennow,
Juha O. Rinne

Affiliations

Anniina Snellman: Turku PET Centre, University of Turku, Turku University Hospital, Turku, Finland; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Corresponding author at: Turku PET Centre, c/o Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland.
Laura L. Ekblad: Turku PET Centre, University of Turku, Turku University Hospital, Turku, Finland
Nicholas J. Ashton: Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway; Department of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK
Thomas K. Karikari: Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Juan Lantero-Rodriguez: Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
Elina Pietilä: Turku PET Centre, University of Turku, Turku University Hospital, Turku, Finland
Mikko Koivumäki: Turku PET Centre, University of Turku, Turku University Hospital, Turku, Finland
Semi Helin: Turku PET Centre, University of Turku, Turku University Hospital, Turku, Finland
Mira Karrasch: Department of Psychology, Åbo Akademi University, Turku, Finland
Henrik Zetterberg: Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at UCL, London, UK; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA
Kaj Blennow: Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Juha O. Rinne: Turku PET Centre, University of Turku, Turku University Hospital, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland

Journal volume & issue: Vol. 183
p. 106175

Abstract

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Plasma phosphorylated tau (p-tau) and glial fibrillary acidic protein (GFAP) both reflect early changes in Alzheimer's disease (AD) pathology. Here, we compared the biomarker levels and their association with regional β-amyloid (Aβ) pathology and cognitive performance head-to-head in clinically unimpaired elderly (n = 88) at three levels of APOE4-related genetic risk for sporadic AD (APOE4/4 n = 19, APOE3/4 n = 32 or non-carriers n = 37). Concentrations of plasma p-tau181, p-tau231 and GFAP were measured using Single molecule array (Simoa), regional Aβ deposition with 11C-PiB positron emission tomography (PET), and cognitive performance with a preclinical composite. Significant differences in plasma p-tau181 and p-tau231, but not plasma GFAP concentrations were present between the APOE4 gene doses, explained solely by brain Aβ load. All plasma biomarkers correlated positively with Aβ PET in the total study population. This correlation was driven by APOE3/3 carriers for plasma p-tau markers and APOE4/4 carriers for plasma GFAP. Voxel-wise associations with amyloid-PET revealed different spatial patterns for plasma p-tau markers and plasma GFAP. Only higher plasma GFAP correlated with lower cognitive scores. Our observations suggest that plasma p-tau and plasma GFAP are both early AD markers reflecting different Aβ-related processes.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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