Accumulation of phosphorylated TDP-43 in brains of patients with argyrophilic grain disease.
To determine whether TAR-DNA binding protein 43 (TDP-43) immunoreactivity was present in brains of argyrophilic grain disease (AGD), we immunohistochemically examined 15 cases of AGD (mean age at death: 84 years) using a panel of anti-TDP-43 antibodies, including both phosphorylation-independent and -dependent ones. Nine AGD cases (60%) showed TDP-43 immunoreactivities mainly in the limbic regions and lateral occipitotemporal cortex. TDP-43 positive structures included neuronal cytoplasmic inclusions, dystrophic neurites, glial cytoplasmic inclusions, grain-like dot-shaped structures, and neurofibrillary tangle (NFT)-like structures. The distribution of these TDP-43 positive structures was largely consistent with that of argyrophilic grains. Double-labeling confocal microscopy revealed, however, that many of phospho-TDP-43 positive structures were not colocalized with phospho-tau staining. Colocalization of phospho-TDP-43 and phospho-tau was observed only in part of neuronal cytoplasmic inclusions, grain-like structures and NFT-like structures. There were no differences in demographics, disease duration, brain weight, NFT Braak stage, or severity of amyloid burden between AGD cases with and without TDP-43-immunoreactivity. However, cases of AGD with TDP-43-immunoreactivity were assigned to higher AGD stages than those without TDP-43-immunoreactivity (P < 0.05). Furthermore, the TDP-43 pathology tended to be prominent in cases with severe grain pathology. The results of the present study indicate for the first time a high frequency of concomitant TDP-43 pathology in AGD, and suggest that abnormal accumulation of TDP-43 may be involved in the pathological process and disease progression of AGD.
Fujishiro
Hiroshige
H
Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
Uchikado
Hirotake
H
Arai
Tetsuaki
T
Hasegawa
Masato
M
Akiyama
Haruhiko
H
Yokota
Osamu
O
Tsuchiya
Kuniaki
K
Togo
Takashi
T
Iseki
Eizo
E
Hirayasu
Yoshio
Y
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism
D004268:DNA-Binding Proteins; D016875:tau Proteins