title: Interrelations between CSF soluble AβPPβ, amyloid-β 1-42, SORL1, and tau levels in Alzheimer's disease.
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.
authors: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors: Panagiotis
authors: P
authors: Alexopoulos
authors: Liang-Hao
authors: LH
authors: Guo
authors: Amalia
authors: A
authors: Tsolakidou
authors: Martina
authors: M
authors: Kratzer
authors: Timo
authors: T
authors: Grimmer
authors: Christine
authors: C
authors: Westerteicher
authors: Meizi
authors: M
authors: Jiang
authors: Hideaki
authors: H
authors: Bujo
authors: Janine
authors: J
authors: Diehl-Schmid
authors: Alexander
authors: A
authors: Kurz
authors: Robert
authors: R
authors: Perneczky
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000134:cerebrospinal fluid*; D008297:Male; D026901:Membrane Transport Proteins / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; D010446:Peptide Fragments; C102582:SORL1 protein, human; C075222:amyloid beta-protein (1-42); D016875:tau Proteins