Albert Dayor Piersson1, Mazlyfarina Mohamad2, Fadilah Rajab3, Subapriya Suppiah4. 1. Diagnostic Imaging and Radiotherapy Programme, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia; Department of Imaging Technology & Sonography, School of Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana. 2. Diagnostic Imaging and Radiotherapy Programme, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia. Electronic address: mazlyfarina@ukm.edu.my. 3. Biomedical Science Programme, Center for Healthy Aging and Wellness, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia. 4. Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia, Selangor 43400, Malaysia.
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.
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.
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