Noche, J. A. | Search bioRxiv

bioRxiv2024

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

INTRODUCTIONUnderstanding relationships between in vivo neurometabolic changes and Alzheimers disease (AD) pathology in the hippocampus, a region vulnerable to early changes in AD, will support early diagnosis. METHODSTwo studies using 1H-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 A{beta}42, 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. RESULTSHippocampal 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 A{beta}42. DISCUSSIONTau deposition in cognitively normal individuals is associated with biochemical changes related to glial reactivity and neural integrity in the hippocampus.

neuroscience↗

bioRxiv2017

Anterolateral entorhinal-hippocampal imbalance in older adults disrupts object pattern separation

The entorhinal cortex (EC) is among the earliest brain areas to deteriorate in Alzheimers disease (AD). However, the extent to which functional properties of the EC are altered in the aging brain, even in the absence of clinical symptoms, is not understood. Recent human fMRI studies have identified a functional dissociation within the EC, similar to what is found in rodents. Here, we used high-resolution fMRI to identify a specific hypoactivity in the anterolateral EC (alEC) commensurate with major behavioral deficits on an object pattern separation task in asymptomatic older adults. Only subtle deficits were found in a comparable spatial condition, with no associated differences in posteromedial EC between young and older adults. We additionally link this condition to previously reported dentate/CA3 hyperactivity, both of which were associated with object mnemonic discrimination impairment. These results provide novel evidence of alEC-dentate/CA3 circuit dysfunction in cognitively normal aged humans.

neuroscience↗