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-? 1-42 (A?42) 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-? protein precursor (A?PP) processing [e.g., soluble A?PP? and ? (sA?PP? and sA?PP?, 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?42, sA?PP?, sA?PP?, 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 ?2. Provided statistically significant differences were detected, multiple linear regression models were employed. Results: A?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?42 concentrations. SORL1, tTau, sA?PP?, and sA?PP? concentrations did not differ between the groups. Conclusion: These findings point to linkages between plaque pathology and glucose cerebral hypometabolism.     «

Background: Biomarker relationships in early stages of Alzheimer's disease (AD) are elusive. Cerebrospinal fluid (CSF) levels of amyloid-? 1-42 (A?42) 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-? protein precursor (A?PP) processing [e.g., soluble A?PP? and ? (sA?PP? and sA?PP?, respectively); sortilin-related receptor with A-type repeats (SORL1, also called LR11 o...     »