Altered Concentrations of Amyloid Precursor Protein Metabolites in the Cerebrospinal Fluid of Patients with Bipolar Disorder

• Published in: Neuropsychopharmacology (New York, N.Y.) N.Y.), 2013-03, Vol.38 (4), p.664-672
• Main Authors: JAKOBSSON, Joel, ZETTERBERG, Henrik, BLENNOW, Kaj, JOHAN EKMAN, Carl, GM JOHANSSON, Anette, LANDEN, Mikael
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Affective disorders; alcohol-use; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer Disease - metabolism; Alzheimer's disease; alzheimers-disease; Amyloid beta-Protein Precursor - cerebrospinal fluid; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein; beta -Amyloid; beta peptides; Biological and medical sciences; Biomarkers; Biomarkers - cerebrospinal fluid; Bipolar disorder; Bipolar Disorder - cerebrospinal fluid; Bipolar Disorder - diagnosis; Bipolar Disorder - metabolism; Bipolar disorders; Cerebrospinal fluid; Cognitive ability; cognitive deficits; Dementia; Depression; dysfunctions; episodes; euthymic patients; Executive function; Female; history; Humans; Kinases; Male; manic; Medical sciences; Medicin och hälsovetenskap; Memory; Mental disorders; metaanalysis; Metabolites; Middle Aged; Mood disorders; Neurochemistry; Neurodegeneration; Neurodegenerative diseases; Neuropsychological Tests; Neurosciences; Neurovetenskaper; Original; Pathophysiology; Physiology; Protein turnover; Proteins; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psykiatri; Schizophrenia; Tau protein
• ISSN: 0893-133X; 1740-634X; 1740-634X
• DOI: 10.1038/npp.2012.231

Bipolar disorder is a psychiatric disorder characterized by recurrent episodes of mania/hypomania and depression. Progressive cognitive dysfunction such as impairments in executive function and verbal memory is common in euthymic bipolar patients. The cerebrospinal fluid has previously been used to study neurodegenerative processes in Alzheimer's disease, from which changes in three core biomarkers have emerged as indicative of degeneration: amyloid β, total tau, and hyperphosphorylated tau. Here, neurodegeneration in bipolar disorder was investigated by assessing the association between bipolar disorder and cerebrospinal fluid biomarkers for neurodegenerative processes. Cerebrospinal fluid was obtained from 139 bipolar disorder patients and 71 healthy controls. Concentrations of total and phosphorylated tau, amyloid β1-42, amyloid β38/β40/β42, and the soluble forms of amyloid precursor protein were measured in patients vs controls. The concentrations of the soluble forms of amyloid precursor protein were significantly lower in bipolar patients compared with controls. The amyloid β42/amyloid β38 and the amyloid β42/amyloid β40 ratios were higher in bipolar patients than controls. There were no discernible differences in the concentrations of total/phosphorylated tau, amyloid β1-42, or amyloid β38/β40/β42. The concentrations of the biomarkers within the bipolar patient group were further associated with different ongoing medical treatments and diagnostic subgroups. The findings suggest that the amyloid precursor protein metabolism is altered in bipolar disorder. The results may have implications for the understanding of the pathophysiology of bipolar disorder and for the development of treatment strategies. Importantly, there were no signs of an Alzheimer-like neurodegenerative process among bipolar patients.