4.7 Article

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

Journal

JOURNAL OF AFFECTIVE DISORDERS
Volume 297, Issue -, Pages 623-633

Publisher

ELSEVIER
DOI: 10.1016/j.jad.2021.10.074

Keywords

Cerebrospinal fluid; Bipolar disorder; Amyloid; Tau; Longitudinal; Case-control; Neurofilament light

Funding

  1. Mental Health Services of Capital of Denmark Research Foundation
  2. AP Moller Foundation for Promotion of Medical Science
  3. Beckett Foundation
  4. King Christian 10th Foundation
  5. Max and Oda Worzner Foundation
  6. Danish Ministry of Health [2007-12143-112, 0901110, 34501, 59506]
  7. Danish Health Foundation [2007B004]

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This case-control study investigated the differences in biomarkers of amyloid and neurodegenerative diseases between patients with bipolar disorder (BD) and healthy control individuals. The results showed a decrease in CSF A beta 42 levels during BD episodes, but no significant differences were found in other markers between BD patients and healthy controls.
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 (A beta) isoforms and ratios (A beta 42, A beta 40, A beta 38), CSF soluble amyloid precursor protein (sAPP) alpha and beta, CSF total (t-tau) and phosphorylated tau (p-tau), CSF neurofilament-light (NF-L), CSF neurogranin (NG), plasma-isoforms A beta 42 and A beta 40, 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 A beta 42 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 A beta 42, A beta 40, A beta 38, A beta 42/38, A beta 42/40, sAPPa, sAPP beta, t-tau, p-tau, p-tau /t-tau, NF-L, NG in CSF and further A beta 40, A beta 42, A beta 42/40, 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 A beta 42 and may suggest an association with brain amyloidosis.

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