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

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 s beta APP beta, a product of the cleavage of the amyloid-beta protein precursor (A beta PP) by beta-secretase, amyloid-beta 1-42 (A beta(42)), soluble SORL1 (also called LR11 or SORLA), a receptor that is involved in A beta PP 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 sA beta PP beta, tau (p < 0.001), and soluble SORL1 (p < 0.001) were detected according to linear regression models. In patients with MCI, sA beta PP beta 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 sA beta PP beta and not tau. A beta(42) 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 A beta oligomers to specifically targeted neurons, resulting in stimulating tau hyperphosphorylation and neurodegeneration.