Interrelations between CSF Soluble AβPPβ, Amyloid-β 1-42, SORL1, and Tau Levels in Alzheimer's Disease

Article type: Research Article

Authors: Alexopoulos, Panagiotis^{a; *} | Guo, Liang-Hao^a | Tsolakidou, Amalia^a | Kratzer, Martina^a | Grimmer, Timo^a | Westerteicher, Christine^a | Jiang, Meizi^b | Bujo, Hideaki^b | Diehl-Schmid, Janine^a | Kurz, Alexander^a | Perneczky, Robert^{a; *}

Affiliations: [a] Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany | [b] Department of Genome Research and Clinical Application, Chiba University, Graduate School of Medicine, Chiba, Japan

Correspondence: [*] Correspondence to: Dr. Panagiotis Alexopoulos or Dr. Robert Perneczky, 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 4214; Fax: +49 89 4140 4888; E-mail: panos.alexopoulos@lrz.tum.de; robert.perneczky@lrz.tum.de.

Abstract: Recently, light has been shed on possible interrelations between the two most important pathological hallmarks of Alzheimer's disease (AD): the amyloid cascade and axonal degeneration. In this study, we investigated associations between sβAPPβ, a product of the cleavage of the amyloid-β protein precursor (AβPP) by β-secretase, amyloid-β 1-42 (Aβ42), soluble SORL1 (also called LR11 or SORLA), a receptor that is involved in AβPP processing, and the marker of axonal degeneration tau in the cerebrospinal fluid (CSF) of 76 patients with mild cognitive impairment (MCI), 61 patients with AD, and 17 patients with frontotemporal dementia, which neuropathologically is not related to the amyloid pathology. In the AD group, significant associations between sAβPPβ, tau (p < 0.001), and soluble SORL1 (p < 0.001) were detected according to linear regression models. In patients with MCI, sAβPPβ correlated significantly with tau (p < 0.001) and soluble SORL1 (p = 0.003). In the FTD group, only SORL1 (p = 0.011) was associated with sAβPPβ and not tau. Aβ42 was found to be significantly related to tau levels in CSF in the MCI group (p < 0.001) and they tended to be associated in the AD group (p = 0.05). Our results provide further evidence for a link between the two facets of AD pathology, which is likely to be mediated by the binding of Aβ oligomers to specifically targeted neurons, resulting in stimulating tau hyperphosphorylation and neurodegeneration.

Keywords: Alzheimer's disease, amyloid, amyloid-β 1-42, association, soluble AβPPβ, SORL1, tau

DOI: 10.3233/JAD-2011-110983

Journal: Journal of Alzheimer's Disease, vol. 28, no. 3, pp. 543-552, 2012