This study's objective was to increase understanding of biological mechanisms underlying clinical Alzheimer's disease (AD) by noninvasively measuring an expanded neurochemical profile and exploring how well this advanced technology distinguishes AD from cognitively normal controls. We measured concentrations of 14 neurochemicals using ultra-high field (7 T) ultra-short echo time (8ms) magnetic resonance spectroscopy (MRS) in 16 participants with mild to moderate clinical AD and 33 age- and gender-matched control participants. MRS was localized to the posterior cingulate cortex (PCC), a region known to be impacted by AD, and the occipital cortex (OCC), a control region. Participants with AD were recruited from dementia specialty clinics. Concentration of the antioxidant ascorbate was higher (p<0.0007) in both brain regions. Concentrations of the glial marker myo-inositol and the choline-containing compounds involved in membrane turnover were higher (p≤0.0004) in PCC of participants with AD. Ascorbate and myo-inositol concentrations were strongly associated, especially in the PCC. Random forests, using the 14 neurochemicals in the two regions, distinguished participants with AD from controls: same-sample sensitivity and specificity were 88% and 97%, respectively, though out-of-sample-values would be lower. Ultra-high field ultra-short echo time MRS identified the co-occurrence of elevated ascorbate and myo-inositol in the PCC as markers that distinguish participants with mild to moderate AD from controls. While elevated myo-inositol may be a surrogate marker of neuroinflammation, the unexpected elevation of the antioxidant ascorbate may reflect infiltration of ascorbate-rich leukocytes.
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Health [grant numbers R01AG039396, P41 EB015894, P30 NS076408] and the W.M. Keck Foundation.
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- myo -inositol
- neurochemical profile
- posterior cingulate cortex
- ultra-high field
- ultra-short echo time