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

Abstract

Background:

Biomarker relationships in early stages of Alzheimer’s disease (AD) are elusive. Cerebrospinal fluid (CSF) levels of amyloid-β 1-42 (Aβ₄₂) 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-β protein precursor (AβPP) processing [e.g., soluble AβPPα and β (sAβPPα and sAβPPβ, 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 Aβ₄₂, sAβPPα, sAβPPβ, 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 χ². Provided statistically significant differences were detected, multiple linear regression models were employed.

Results:

Aβ₄₂ 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 Aβ₄₂ concentrations. SORL1, tTau, sAβPPα, and sAβPPβ concentrations did not differ between the groups.

Conclusion:

These findings point to linkages between plaque pathology and glucose cerebral hypometabolism.