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

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.

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.

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.

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.