Interactions between Amyloid-β and Tau in Cerebrospinal Fluid of People with Mild Cognitive Impairment and Alzheimer's Disease

Issue title: 2013 International Congress on Vascular Dementia

Guest editors: Amos D. Korczyn

Article type: Research Article

Authors: Kristofikova, Zdena^{a; *} | Ricny, Jan^a | Kolarova, Michaela^a | Vyhnalek, Martin^{b; c} | Hort, Jakub^{b; c} | Laczo, Jan^{b; c} | Sirova, Jana^a | Ripova, Daniela^a

Affiliations: [a] Prague Psychiatric Center, Prague, Czech Republic | [b] Memory Disorders Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic | [c] International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic

Correspondence: [*] Correspondence to: Zdena Kristofikova, Alzheimer Disease Center, Prague Psychiatric Center, Ustavni 91, 181 03 Prague 8 – Bohnice, Czech Republic. Tel.: +420 266 003 164; Fax: +420 266 003 160; E-mail: kristofikova@pcp.lf3.cuni.cz.

Abstract: Background:Despite the physiological sequestration of amyloid-β (Aβ) peptides by various carriers, interactions between peptides and protein tau appear to be pathological and involved in the development of Alzheimer’s disease (AD). A recent study reported increased Aβ-tau interactions in the neurons of AD patients. Objective:We investigated the possibility that levels of Aβ-tau complexes in cerebrospinal fluid could be a prospective biomarker of AD, with greater sensitivity and specificity than Aβ1-42, tau, or phospho-tau individually. Methods:By means of ELISA, we estimated levels of the complexes in 161 people (non-demented controls, people with mild cognitive impairment (MCI), probable AD or other types of dementia). Results:We found significant reductions in levels in people with MCI due to AD (down to 84.5%) or with AD (down to 80.5%) but not in other types of dementia. The sensitivity of the new biomarker to AD was 68.6%, the specificity 73.3% (compared to controls) or 59.1–66.1% (compared to other types of dementia). No significant correlations were observed between the complexes and the remaining biomarkers or between those and Mini-Mental State Examination score. Conclusion:We suppose that attenuated levels of complexes in cerebrospinal fluid reflect the accumulation of Aβ bound to tau in AD neurons and that changes start many years before symptom onset, analogously to those in Aβ1-42, tau, or phospho-tau. Unfortunately, these complexes are not a significantly better biomarker of AD than current biomarkers.

Keywords: Amyloid-β peptides, biomarker, cerebrospinal fluid, interactions, tau protein

DOI: 10.3233/JAD-132393

Journal: Journal of Alzheimer's Disease, vol. 42, no. s3, pp. S91-S98, 2014