Excitatory amino acid transporter 2 associates with phosphorylated tau and is localized in neurofibrillary tangles of tauopathic brains.
Phosphorylated tau (p-tau) is the principal component of neurofibrillary tangles, a pathological hallmark, and likely plays a neurotoxic role in tauopathies including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). We subjected brains from autopsy cases of AD, PSP, and CBD to a variety of immunohistochemical, immunoblotting, and pull-down assays. In this study, we show that excitatory amino acid transporter 2 (EAAT2) preferentially interacted with phosphorylated tau and was localized in neurofibrillary tangles in the brains of such patients. These results strongly indicate that EAAT2 acts in tauopathy-related neurodegeneration, and abnormalities in glutamate transport play an important role in the pathogenesis of tauopathies.
Sasaki
Kumi
K
Department of Neurology, Juntendo University, Urayasu Hospital, Tokyo, Japan.
Shimura
Hideki
H
Itaya
Masako
M
Tanaka
Ryota
R
Mori
Hideo
H
Mizuno
Yoshikuni
Y
Kosik
Kenneth S
KS
Tanaka
Shigeki
S
Hattori
Nobutaka
N
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D027342:Excitatory Amino Acid Transporter 2 / Q000032:analysis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D024801:Tauopathies / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism*
D027342:Excitatory Amino Acid Transporter 2; D016875:tau Proteins