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

Background: Biomarker relationships in early stages of Alzheimer's disease (AD) are elusive. Cerebrospinal fluid (CSF) levels of amyloid-beta 1-42 (A beta(42)) and total tau (tTau) as well as F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) contribute to help unravel AD pathology. Furthermore, peptides related to amyloid-beta protein precursor (A beta PP) processing [e.g., soluble A beta PP alpha and beta (sA beta PP alpha and sA beta PP beta, 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 A beta(42), sA beta PP alpha, sA beta PP beta, 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 chi(2). Provided statistically significant differences were detected, multiple linear regression models were employed. Results: A beta(42) 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 A beta(42) concentrations. SORL1, tTau, sA beta PP alpha, and sA beta PP beta concentrations did not differ between the groups. Conclusion: These findings point to linkages between plaque pathology and glucose cerebral hypometabolism.