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THE RELATIONSHIP OF ELEVATED MEDIAL TEMPORAL LOBE AND DIFFUSE BRAIN TAU-PET SIGNAL IN CLINICALLY NORMAL PARTICIPANTS

      Background

      Medial temporal lobe (MTL) uptake on tau-PET is seen in AD dementia but also in the aging population. Some AD dementia patients have much less MTL tau-PET signal compared to other isocortical signal. The relationship of these findings to the development of AD dementia needs to be better understood.

      Methods

      Tau-PET with AV-1451 was performed on 439 cognitively normal (CN) participants ages 50-94. For each cortical region we defined abnormal tau-PET as cortical to cerebellar crus grey matter ratio (SUVr) greater than the 95th percentile among 71 CN participants ages 30-49. We included entorhinal cortex, parahippocampal gyrus, and hippocampus as MTL regions. All other cortical regions were considered extra-MTL regions. Off-target regions, such as pallidum, were excluded. The number of CNs with and without abnormal MTL regions and those with or without extra-MTL abnormalities were determined. We characterized the age, PiB and APOE status of the groups.

      Results

      Of CN participants, 37% (163/439) had MTL abnormalities. Of those with MTL findings, 95% (155/163) had extra-MTL abnormality with most having more than one (Figure 1). Of the 276 without an MTL abnormality, 29% (81/276) had extra-MTL abnormalities (Figure 2). Participants having MTL abnormalities tended to be older (p<0.001) and have elevated amyloid (p<0.001). Among those having MTL abnormalities, no age or PIB differences were seen between those with or without extra-temporal abnormalities. There were no significant differences in the percentage of APOE e4 carriers.

      Conclusions

      MTL tau-PET signal is often associated with abnormal extra-MTL tau-PET signal in CN participants and likely represents neurofibrillary tangle development in participants likely to develop AD dementia. Tau-PET signal exclusively outside of the MTL is seen in 29% of CN participants and could be the initial finding in a unique subset of participants in the AD dementia pathway. These findings need to be evaluated with longitudinal data.
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      Figure 1Numeric distribution of regional abnormalities outside medial temporal lobe (MTL) among those having any MTL abnormality.
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      Figure 2Numeric distribution of regional abnormalities outside medial temporal lobe (MTL) among those having any MTL abnormality.