Amyloid Cascade and Tau Pathology Cerebrospinal Fluid Markers in Mild Cognitive Impairment with regards to Alzheimer's Disease Cerebral Metabolic Signature

Article type: Research Article

Authors: Alexopoulos, Panagiotis^{a; *} | Guo, Liang-Hao^a | Jiang, Meizi^b | Bujo, Hideaki^b | Grimmer, Timo^a | Förster, Stefan^{c; d} | Drzezga, Alexander^{c; e} | Kurz, Alexander^a | Perneczky, Robert^{a; f}

Affiliations: [a] Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany | [b] Department of Genome Research and Clinical Application, Chiba University, Graduate School of Medicine, Chiba, Japan | [c] Department of Nuclear Medicine, Technische Universität München, Munich, Germany | [d] TUM Neuroimaging Center (TUM-NIC), Technische Universität München, Munich, Germany | [e] Klinik und Poliklinik für Nuklearmedizin, Uniklinik Köln, Cologne, Germany | [f] Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology and Medicine, London, UK

Correspondence: [*] Correspondence to: Dr. Panagiotis Alexopoulos, Klinik und Poliklinik für Psychiatrie und Psychotherapie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München, Germany. Tel.: +49 89 4140 5506; Fax: +49 89 4140 4243; E-mail: [email protected].

Abstract: Background:Biomarker relationships in early stages of Alzheimer’s disease (AD) are elusive. Cerebrospinal fluid (CSF) levels of amyloid-β 1-42 (Aβ42) and total tau (tTau) as well as 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) contribute to help unravel AD pathology. Furthermore, peptides related to amyloid-β protein precursor (AβPP) processing [e.g., soluble AβPPα and β (sAβPPα and sAβPPβ, respectively); sortilin-related receptor with A-type repeats (SORL1, also called LR11 or SORLA)] are factors crucially implicated in the formation of pathological hallmarks of AD. Objective:To unveil differences in CSF concentrations of Aβ42, sAβPPα, sAβPPβ, tTau, and SORL1 between patients with mild cognitive impairment (MCI) who were categorized according to expert interpretation of FDG scans. Methods:PET results were classified as suggesting high likelihood for AD (MCI-AD high), intermediate likelihood for AD (MCI-AD intermediate), or little likelihood for AD (MCI-AD unlikely). An AD dementia group was also included. Differences between the groups were tested by Kruskal- Wallis test, Mann-Whitney test, or χ2. Provided statistically significant differences were detected, multiple linear regression models were employed. Results:Aβ42 levels in patients with MCI-AD high (n = 15) were lower compared to MCI-AD intermediate (n = 18) and MCI-AD unlikely patients (n = 25) (p = 0.002), while they did not differ from patients with AD dementia (n = 17). The regression model revealed a significant impact of the metabolic pattern on Aβ42 concentrations. SORL1, tTau, sAβPPα, and sAβPPβ concentrations did not differ between the groups. Conclusion:These findings point to linkages between plaque pathology and glucose cerebral hypometabolism.

Keywords: Amyloid-β, mild cognitive impairment, sAβPPα, sAβPPβ, SORL1, total tau

DOI: 10.3233/JAD-122329

Journal: Journal of Alzheimer's Disease, vol. 36, no. 2, pp. 401-408, 2013