Affiliations: [a] Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, Erlangen, Germany | [b] Institute of Medical Informatics, University of Erlangen-Nuremberg, Erlangen, Germany | [c] Department of Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany
Correspondence:
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Correspondence to: PD Dr. med. Piotr Lewczuk, Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Department of Psychiatry and Psychotherapy, Schwabachanlage 6, 91054 Erlangen, Germany. Tel.: +49 9131 85 34324; Fax: +49 9131 85 238; E-mail: Piotr.Lewczuk@uk-erlangen.de.
Note: [] Handling Associate Editor: Henrik Zetterberg
Abstract: Neurochemical Dementia Diagnostics (NDD), i.e., analysis of the cerebrospinal fluid (CSF) concentrations of amyloid-β peptides and tau/phospho-tau proteins plays important role in the diagnosis of neurodegeneration and dementias. Several studies show alterations of these biomarkers in Alzheimer's disease (AD), however, only a few reports address alterations of other CSF biomarkers (albumin and immunoglobulins' quotients, cell count, lactate concentration, etc.) in the pathophysiology and diagnostic procedures of dementias. Therefore, we analyzed these biomarkers in patients diagnosed for dementia syndromes and carefully characterized with the state-of-the-art NDD analysis: Aβ1–42, Aβx–42, Aβx–42/x–40 ratio, tau, and ptau181. We found intrathecal IgG synthesis in 5 out of 112 patients showing alterations of the NDD biomarkers, and in four out of these five subjects, we could not find any satisfying reason for the intrathecal humoral response. In 25.9% of the patients with altered NDD biomarkers, we found an increased albumin quotient indicating a dysfunction of the blood-CSF barrier; however a similar figure of 25.2% was found in the group of patients without alterations in the NDD. Our findings suggest that at least some patients with increased CSF concentrations of tau/ptau proteins and decreased concentrations of Aβ42 peptides show simultaneously CSF alterations found otherwise in neuroinflammatory processes. This, in turn, suggests that extended diagnosis should be performed in patients with “isolated” alterations of NDD biomarkers or intrathecal immunoglobulin synthesis.
Keywords: Amyloid-β, cerebrospinal fluid, dementia, neurodegeneration, neuroimmunology, tau
