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

Ulla Knorr; Anja Hviid Simonsen; Camilla Steen Jensen; Henrik Zetterberg; Kaj Blennow; Morten Akhøj; Julie Forman; Steen Gregers Hasselbalch; Lars Vedel Kessing

doi:10.1016/j.jad.2021.10.074

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

Ulla Knorr^*, Anja Hviid Simonsen, Camilla Steen Jensen, Henrik Zetterberg, Kaj Blennow, Morten Akhøj, Julie Forman, Steen Gregers Hasselbalch, Lars Vedel Kessing

^*Corresponding author for this work

17 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Affective Disorders
Volume	297
Pages (from-to)	623-633
Number of pages	11
ISSN	0165-0327
DOIs	https://doi.org/10.1016/j.jad.2021.10.074
Publication status	Published - 15 Jan 2022

Keywords

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

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10.1016/j.jad.2021.10.074

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@article{ac81d2576fc54f418709a89cdfce7be2,

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

abstract = "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.",

keywords = "Amyloid, Bipolar disorder, Case-control, Cerebrospinal fluid, Longitudinal, Neurofilament light, Tau",

author = "Ulla Knorr and Simonsen, {Anja Hviid} and Jensen, {Camilla Steen} and Henrik Zetterberg and Kaj Blennow and Morten Akh{\o}j and Julie Forman and Hasselbalch, {Steen Gregers} and Kessing, {Lars Vedel}",

note = "Copyright {\textcopyright} 2021. Published by Elsevier B.V.",

year = "2022",

month = jan,

day = "15",

doi = "10.1016/j.jad.2021.10.074",

language = "English",

volume = "297",

pages = "623--633",

journal = "Journal of Affective Disorders",

issn = "0165-0327",

publisher = "Elsevier BV",

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TY - JOUR

T1 - Alzheimer's disease related biomarkers in bipolar disorder - A longitudinal one-year case-control study

AU - Knorr, Ulla

AU - Simonsen, Anja Hviid

AU - Jensen, Camilla Steen

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Akhøj, Morten

AU - Forman, Julie

AU - Hasselbalch, Steen Gregers

AU - Kessing, Lars Vedel

PY - 2022/1/15

Y1 - 2022/1/15

N2 - 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.

AB - 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.

KW - Amyloid

KW - Bipolar disorder

KW - Case-control

KW - Cerebrospinal fluid

KW - Longitudinal

KW - Neurofilament light

KW - Tau

UR - http://www.scopus.com/inward/record.url?scp=85118530255&partnerID=8YFLogxK

U2 - 10.1016/j.jad.2021.10.074

DO - 10.1016/j.jad.2021.10.074

M3 - Journal article

C2 - 34728295

SN - 0165-0327

VL - 297

SP - 623

EP - 633

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

ER -

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

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Keywords

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