Biomarkers

Maciej Dulewicz; Przemyslaw Radoslaw Kac; Fernando Gonzalez-Ortiz; Thomas K Karikari; Agnieszka Kulczynska-Przybik; Barbara Mroszko; Michael Turton; Peter Harrison; Juan Manuel Maler; Timo Jan Oberstein; Johannes Kornhuber; Jörg Hanrieder; Henrik Zetterberg; Kaj Blennow; Piotr Lewczuk

doi:10.1002/alz.090819

Biomarkers

Alzheimers Dement. 2024 Dec:20 Suppl 2:e090819. doi: 10.1002/alz.090819.

Authors

Maciej Dulewicz¹, Przemyslaw Radoslaw Kac², Fernando Gonzalez-Ortiz³, Thomas K Karikari^{4

5}, Agnieszka Kulczynska-Przybik⁶, Barbara Mroszko⁷, Michael Turton⁸, Peter Harrison⁸, Juan Manuel Maler⁹, Timo Jan Oberstein⁹, Johannes Kornhuber¹⁰, Jörg Hanrieder^{11

12}, Henrik Zetterberg^{13

14

15

16

17

18}, Kaj Blennow^{19

20}, Piotr Lewczuk^{9

21}

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Gothenburg, Sweden.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
³ Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.
⁴ Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, PA, Sweden.
⁵ University of Pittsburgh, Pittsburgh, PA, USA.
⁶ Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Bialystok, Poland.
⁷ Department of Neurodegeneration Diagnostics, Medical University of Białystok, Poland, Bialystok, Poland.
⁸ Bioventix Plc, Farnham, United Kingdom.
⁹ Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
¹⁰ University hospital Erlangen, Friedrich-Alexander-University Erlangen Nuremberg, Erlangen, Germany.
¹¹ Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
¹² Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
¹³ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
¹⁴ Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁵ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, -, United Kingdom.
¹⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Gothenburg, Sweden.
¹⁷ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
¹⁸ UK Dementia Research Institute at UCL, London, United Kingdom.
¹⁹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
²⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
²¹ Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.

PMID: 39786142
DOI: 10.1002/alz.090819

Abstract

Background: In the context of Alzheimer's disease (AD), blood-based biomarkers have become increasingly important for various clinical purposes, such as screening patients and tracking the progression of the disease. Tau is a protein that stabilizes microtubules in nerve cells. In AD, different isoforms of tau become hyperphosphorylated, leading to the formation of neurofibrillary tangles, which are a key pathological feature of the AD. Measuring levels of different phosphorylated tau in the blood can provide insights into the extent of tau pathology in the brain. Phosphorylated tau (pTau) serves as a blood biomarker signaling the existence of AD-related alterations, with pTau217, pTau181, and pTau231 proving to be significant indicators in this context. The primary goal of this study is to investigate the diagnostic utility of measuring plasma pTau217, pTau181 and pTau231 levels in identifying possible AD cases. This study intends to evaluate how effectively the concentrations of pTau217, pTau181 and pTau231 in the blood can differentiate individuals with CSF biomarker-confirmed AD in comparison to CSF biomarker-negative control group.

Method: Plasma concentrations of pTau217, pTau181 and pTau231 were measured by in-house Single molecule array (Simoa) assays developed at the University of Gothenburg (UGOT p-tau217, pTau181 and pTau231). The quantitative assessment of classical biomarkers (Aβ-42, Aβ-42/Aβ-40, tTau, and pTau181) in the CSF of patients with possible AD according to the Erlangen Score algorithm (ER 2 and 3) and controls (ER 0) were performed by Lumipulse.

Result: Significantly The levels of pTau217, pTau181 and pTau231 correlated positively with CSF tTau, pTau181 and negatively with CSF Aβ1-42 and Aβ ratio. The greatest effect size was observed for pTau217 (d=1.63), moderate for pTau181 (d=0.57) and pTau231 (d=0.3) respectively.

Conclusion: The results of the present study indicate that plasma pTau217 could be the most valuable blood biomarker for AD diagnosis among the tested isoforms.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease* / blood
Alzheimer Disease* / diagnosis
Amyloid beta-Peptides* / blood
Amyloid beta-Peptides* / cerebrospinal fluid
Biomarkers* / blood
Biomarkers* / cerebrospinal fluid
Female
Humans
Male
Middle Aged
Peptide Fragments / blood
Peptide Fragments / cerebrospinal fluid
Phosphorylation
tau Proteins* / blood
tau Proteins* / cerebrospinal fluid

Substances

tau Proteins
Biomarkers
Amyloid beta-Peptides
Peptide Fragments
amyloid beta-protein (1-42)