@misc{oai:repo.qst.go.jp:00085539,
 author = {Kiwamu, Matsuoka and Kosei, Hirata and Naomi, Kokubo and Kenji, Tagai and Hironobu, Endo and Keisuke, Takahata and Hitoshi, Shinoto and Maiko, Ono and Chie, Seki and Kazunori, Kawamura and Zhang, Ming-Rong and Hitoshi, Shimada and Makoto, Higuchi and Kiwamu, Matsuoka and Kosei, Hirata and Naomi, Kokubo and Kenji, Tagai and Hironobu, Endo and Keisuke, Takahata and Hitoshi, Shinoto and Maiko, Ono and Chie, Seki and Kazunori, Kawamura and Zhang, Ming-Rong and Hitoshi, Shimada and Makoto, Higuchi},
 month = {Mar},
 note = {Objective: Despite accumulating evidence for impaired glutamatergic neurotransmission in Alzheimer’s disease (AD) brains, its significance in neurofunctional and neuropathological alterations remains elusive. The aim of this study is to evaluate the associations between glutamatergic dysfunctions and tau depositions across cortical regions in AD patients using magnetic resonance spectroscopic imaging (MRSI).
Methods: We enrolled 16 patients with AD, consisting of cases with mild cognitive impairment due to AD and AD dementia, and 15 healthy controls (HCs). We performed tau and amyloid-β (Aβ) PET with 18F-PM-PBB3 and 11C-PiB, respectively, and single-plane MRSI for evaluating a glutamate/creatine (Glu/Cr) ratio at the level of the cingulate gyrus. PET probe retentions were quantified as standardized uptake value ratio (SUVR) using the cerebellar cortex as a reference region.
Results: Z-score maps of the AD group compared to the HC group showed marked tau and Aβ depositions in extensive cortical gray matter regions, and reduced glutamate levels in more confined areas (Figures 1-3). Glutamate levels were correlated with tau but not Aβ burdens in some regions, including the posterior cingulate cortex (PCC) (Figures 4). In an analysis of combined voxels covering PCC, Glu/Cr ratios were correlated negatively with tau deposits in the AD group (r = -0.53, p < 0.05) and positively with mini-mental state examination scores (r = 0.74, p < 0.05) in AD dementia cases.
Conclusions: MRSI revealed the regionally variable vulnerability of the glutamatergic system to tau depositions in AD brains. In PCC, tau accumulations are likely to induce disrupted glutamine transmissions, aggravating cognitive functions., AD/PD 2022},
 title = {Magnetic resonance spectroscopic imaging enables spatial mapping of decreased glutamate levels associated with tau depositions in Alzheimer’s disease brains},
 year = {2022}
}