Alzheimer's disease related biomarkers in bipolar disorder – A longitudinal one-year case-control study

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Introduction: Bipolar disorder (BD) is a heterogeneous mental disorder characterized by recurrent relapses of affective episodes: Subgroups of patients with BD have cognitive deficits, and an increased risk of dementia. Methods: This prospective, longitudinal, one-year follow-up, case-control study investigated biomarkers for AD and neurodegenerative diseases, namely: cerebrospinal fluid (CSF) amyloid beta (Aβ) isoforms and ratios (Aβ42, Aβ40, Aβ38), CSF soluble amyloid precursor protein (sAPP) α and β, CSF total (t-tau) and phosphorylated tau (p-tau), CSF neurofilament-light (NF-L), CSF neurogranin (NG), plasma-isoforms Aβ42 and Aβ40, plasma-tau, plasma-NF-L, and serum S100B, in patients with BD (N = 62, aged 18–60) and gender-and-age-matched healthy control individuals (N = 40). CSF and plasma/serum samples were collected at baseline, during and after an affective episode, if it occurred, and after a year. Data were analyzed in mixed models. Results: Levels of CSF Aβ42 decreased in patients with BD who had an episode during follow-up (BD-E) (N = 22) compared to patients without an episode (BD-NE) (N = 25) during follow-up (P = 0.002). Stable levels were seen for all other markers in BD-E compared to BD-NE during the one-year follow-up. We found no statistically significant differences between patients with BD and HC at T0 and T3 for Aβ42, Aβ40, Aβ38, Aβ42/38, Aβ42/40, sAPPα, sAPPβ, t-tau, p-tau, p-tau /t-tau, NF-L, NG in CSF and further Aβ40, Aβ42, Aβ42/40, t-tau, NF-L in plasma, S100B in serum, and APOE-status. Furthermore, all 18 biomarkers were stable in HC during the one-year follow-up from T0 to T3. Conclusion: A panel of biomarkers of Alzheimer's and neurodegeneration show no differences between patients with BD and HC. There were abnormalities of amyloid production/clearance during an acute BD episode. The abnormalities mimic the pattern seen in AD namely decreasing CSF Aβ42 and may suggest an association with brain amyloidosis.

OriginalsprogEngelsk
TidsskriftJournal of Affective Disorders
Vol/bind297
Sider (fra-til)623-633
Antal sider11
ISSN0165-0327
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
We thank the participants for their contribution to the study. The study was supported by The Mental Health Services of Capital of Denmark Research Foundation, AP Møller Foundation for Promotion of Medical Science, The Beckett Foundation, The King Christian 10th Foundation and the Max and Oda Wørzner Foundation (recipient author U.K.). The Danish Dementia Research Center is supported by grants from the Danish Ministry of Health (J No. 2007–12143–112, project 59506/J No. 0901110, project 34501) and the Danish Health Foundation (J No. 2007B004). The funding sources of the study had no role in study design; in the collection, analysis and interpretation of data; in writing of the report; and in the decision to submit the paper for publication.

Funding Information:
We thank the participants for their contribution to the study. The study was supported by The Mental Health Services of Capital of Denmark Research Foundation, AP M?ller Foundation for Promotion of Medical Science, The Beckett Foundation, The King Christian 10th Foundation and the Max and Oda W?rzner Foundation (recipient author U.K.). The Danish Dementia Research Center is supported by grants from the Danish Ministry of Health (J No. 2007?12143?112, project 59506/J No. 0901110, project 34501) and the Danish Health Foundation (J No. 2007B004). The funding sources of the study had no role in study design; in the collection, analysis and interpretation of data; in writing of the report; and in the decision to submit the paper for publication. Ulla Knorr has been a consultant for AstraZeneca in 2013. Anja Hviid Simonsen and Steen Hasselbalch declare no conflicts of interests. Henrik Zetterberg has served at advisory boards of Eli Lilly, Roche Diagnostics, has received travel support from TEVA, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. Dr. Blennov has served as a consultant or at advisory boards for Alzheon, BioArtic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Pfizer, and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB. Lars Vedel Kessing has within the preceding three years been a consultant for Sunovion.

Publisher Copyright:
© 2021

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