Cerebrospinal Fluid Amyloid Beta, Tau Levels, Apolipoprotein, and 1H-MRS Brain Metabolites in Alzheimer's Disease: A Systematic Review

Abstract

Background: There is compelling evidence that neurochemical changes measured by proton magnetic resonance spectroscopy (¹H-MRS) occur at different phases of Alzheimer's disease (AD). However, the extent to which these neurochemical changes are associated with validated AD biomarkers and/or apolipoprotein (APOE) ε4 is yet to be established.

Objective: This systematic review analyzed the available evidence on (1) neurochemical changes; and (2) the relations between brain metabolite and validated cerebrospinal fluid biomarkers, and/or APOE in AD.

Methods: PubMed, Cochrane, Scopus, and gray literature were systematically screened for studies deemed fit for the purpose of the current systematic review.

Results: Twenty four articles met the inclusion criteria. Decreased levels of N-acetyl aspartate (NAA), NAA/(creatine) Cr, and NAA/(myo-inositol) ml, and increased ml, ml/Cr, Cho (choline)/Cr, and ml/NAA were found in the posterior cingulate cortex/precuneus. Increased ml is associated with increased tau levels, reduced NAA/Cr is associated with increased tau. ml/Cr is negatively correlated with Aβ42, and ml/Cr is positively correlated with t-tau. NAA and glutathione levels are reduced in APOE ε4 carriers. APOE ε4 exerts no modulatory effect on NAA/Cr. There is interaction between APOE ε4, Aβ42, and ml/Cr.

Conclusion: NAA, ml, NAA/Cr, NAA/ml and ml/Cr may be potentially useful biomarkers that may highlight functional changes in the clinical stages of AD. The combinations of ml and tau, NAA/Cr and Aβ42, and NAA/Cr and tau may support the diagnostic process of differentiating MCI/AD from healthy individuals. Large, longitudinal studies are required to clarify the effect of APOE ε4 on brain metabolites.

Keywords: Alzheimer's disease; Amyloid beta; Apolipoprotein; Proton magnetic resonance spectroscopy; Tau; cerebrospinal fluid.