Myo-inositol and total NAA in the hippocampus are linked to CSF tau pathology in cognitively normal older adults

INTRODUCTION Understanding relationships between in vivo neurometabolic changes and Alzheimer’s disease (AD) pathology in the hippocampus, a region vulnerable to early changes in AD, will support early diagnosis. METHODS Two studies using 1 H-MRS examined concentrations of myo-inositol (MI), total creatine (tCr) and total NAA (tNAA) in the hippocampus. The first study compared hippocampal metabolite concentrations in healthy young and older adults and the second study assessed relationships between hippocampal metabolites and cerebrospinal fluid (CSF) measurements of Aβ42, phosphotau 181 (pTau181), and total tau (t-Tau) while adjusting for demographic covariates and spectral characteristics (linewidth, signal- to-noise ratio) in a separate group of older adults ranging from cognitively normal (CN) to AD-dementia. RESULTS Hippocampal MI, but not tCr or tNAA, was increased in cognitively normal older versus young adults. Within the second older adult group, MI and tNAA, but not tCr, were linked to increases in CSF pTau181 and t-Tau, but not Aβ42. DISCUSSION Tau deposition in cognitively normal individuals is associated with biochemical changes related to glial reactivity and neural integrity in the hippocampus.