Amyloid-Negative Dementia in the Elderly is Associated with High Accumulation of Tau in the Temporal Lobes

Jun Takeuchi1, Takayuki Kikukawa1, Haruna Saito1, Itsuki Hasegawa1, Akitoshi Takeda1, Hiroyuki Hatsuta1, Joji Kawabe2, Yasuhiro Wada3, Aya Mawatari3, Ami Igesaka3, Hisashi Doi3, Yasuyoshi Watanabe3, Hitoshi Shimada4, Soichiro Kitamura4, Makoto Higuchi4, Tetsuya Suhara4, Yoshiaki Itoh1, *
1 Department of Neurology, Osaka City University Graduate School of Medicine, Asahimachi 1-4-3, Abenoku, Osaka, japan
2 Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
3 RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
4 Department of Functional Brain Imaging Research (DOFI), Clinical Research Cluster, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan

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© 2019 Takeuchi et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: ( This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Neurology, Osaka City University Graduate School of Medicine, Asahimachi 1-4-3, Abenoku, Osaka, Japan; Tel: +81666465599; Email:



We previously reported that among cases clinically diagnosed with Alzheimer’s disease, the proportion of amyloid beta (Aβ) -negative case increases in the elderly population. Tauopathy including Argyrophilic Grain Disease (AGD) and Neurofibrillary Tangle-Predominant Dementia (NFTPD), may be the leading causes of such dementia.


To evaluate the involvement of tau, we studied tau accumulation in Amyloid-Negative Dementia Cases in the Elderly (ANDE) with Positron Emission Tomography (PET).


Seven cases with slowly progressive dementia who were older than 80 years and were negative for Aβ were studied. In one case, autopsy obtained 2 years after the PET examination revealed neurofibrillary tangles limited around the parahippocampal gyrus. Four cases showed strong laterality in magnetic resonance imaging atrophy (clinical AGD), while the other three cases had no significant laterality in atrophy (clinical NFTPD). Age-corrected PET data of healthy controls (HC; n = 12) were used as control. Tau accumulation was evaluated with [11C]PBB3-PET.


High accumulation was found in the lateral temporal cortex in ANDE. In autopsy case, scattered neurofibrillary tangles were found in the parahippocampal gyrus. In addition, there was a very high accumulation of PBB3 in the large area of bilateral parietal lobes, although no corresponding tau component was found in the autopsied case.


Relatively high burden of tau deposition was commonly observed in the lateral temporal cortex and parietal cortex of ANDE, part of which may explain dementia in these subjects. [11C]PBB3 may be useful in detecting tauopathy in ANDE.

Keywords: Amyloid PET, [11C]PBB3, Dementia, Elderly, Positron Emission Tomography, Tau PET.