Tau accumulation in the nucleus accumbens in tangle-predominant dementia.
BACKGROUND
Tangle-predominant dementia (TPD) is characterized neuropathologically by numerous neurofibrillary tangles in the limbic areas with no or occasional senile plaques throughout the brain. TPD is an under-recognized disease, while it is a common cause of dementia in those over 80 years of age. In the present study, we describe hyperphosphorylated tau (tau) accumulation in the nucleus accumbens (Acb) in patients with TPD.


RESULTS
We investigated immunohistochemically the brain tissues from 7 patients with TPD, 22 with Alzheimer disease (AD) and 11 non-demented aged subjects. In the Acb of all 7 TPD patients, a considerable number of tau positive neurons were found together with many neuropil threads. The tau deposits in the Acb were labeled with all the anti-tau antibodies used in the present study. They included conformational change-specific, phosphorylation-specific and phosphorylation-independent antibodies. The Acb consists of the predominant medium-sized neurons with a small number of large neurons. Both the cell types were affected by tau pathology in TPD. Tau accumulation in the majority of such neurons appeared to be pretangle-like, diffuse deposits with only occasional paired helical filament formation. Tau positive neurons were also found in the Acb in some AD and non-demented aged subjects but much fewer in the majority of cases. The immunoblot analyses of fresh frozen samples of the Acb and parahippocampal cortex from 3 TPD and 3 AD patients revealed that the insoluble tau in the Acb was a mixture of the 3- and 4-repeat isoforms.


CONCLUSIONS
To our knowledge, this is the first report on the occurrence of tau accumulation in the Acb in TPD. The Acb receives direct and massive projections from the hippocampal CA1 and subiculum where neurofibrillary tangles are known to occur more frequently in TPD than in AD. The prevalence of abnormal tau accumulation in the Acb in TPD may support the idea that abnormal tau aggregation propagates via neural circuits. In all but one TPD cases used in this study, delusion was a consistent clinical feature. Whether the Acb tau accumulation is related to the psychiatric symptoms in TPD may be an issue for further investigation.
Ito
I
Kawakami
Masato
M
Hasegawa
Tetsuaki
T
Arai
Kenji
K
Ikeda
Kenichi
K
Oshima
Kazuhiro
K
Niizato
Naoya
N
Aoki
Katsuse
K
Omi
Shinji
S
Higashi
Masato
M
Hosokawa
Yoshio
Y
Hirayasu
Dementia Research Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. akiyama-hr@igakuken.or.jp.
Haruhiko
H
Akiyama
D000368:Aged; D000369:Aged, 80 and over; D003704:Dementia / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology*; D009474:Neurons / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins