Elevated cerebrospinal fluid tau protein levels in Wernicke's encephalopathy.
OBJECTIVE
Limited neuronal cell loss is seen in the neuropathology of Wernicke's encephalopathy (WE), but the extent of neuronal damage has not been well studied. Moreover, there is still a debate as to whether alcohol itself causes brain damage in humans. Although, it is difficult to examine the extent of neuronal damage in living patients, recent studies have revealed that total tau protein levels in the cerebrospinal fluid (CSF) reflect the rate of neuronal degeneration. Therefore, we hypothesized that the elevated CSF total tau in patients with WE was due to neuronal damage and thus we examined CSF total tau protein in patients with WE, as well as in those with alcohol withdrawal delirium (WD) and Korsakoff syndrome (KS). We also examined CSF total tau in nonalcohol dependent patients with Alzheimer's disease (AD) as a disease control.


METHODS
CSF samples were obtained from 13 acute WE patients with alcohol dependence, 9 WD patients with alcohol dependence and 16 KS patients with alcohol dependence, and from 20 nonalcohol dependent AD patients. CSF was also obtained from 10 of the WE patients after their disease had progressed to the chronic stage. CSF tau protein levels in all samples were determined by sandwich enzyme-linked immunosorbent assay. Tau phosphorylated at threonine 181 (p-tau(181)) and amyloid beta-protein ending at amino acid 42 (A beta 42) in CSF were also determined for comparison between acute WE with AD.


RESULTS
Total tau was significantly elevated in acute WE and decreased on long-term follow-up, but was not elevated in WD or KS. The patterns of p-tau(181) and A beta 42 differed between acute WE and AD.


CONCLUSIONS
Intense neuronal cell death occurs transiently in WE, and the mechanism differs from that in AD. Neuronal damage is generally unaccompanied in WD. These results suggest that CSF total tau is a useful biological marker for WE.
Matsushita
Sachio
S
National Hospital Organization, Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan. shiguchi@wa2.so-net.ne.jp
Miyakawa
Tomohiro
T
Maesato
Hitoshi
H
Matsui
Toshifumi
T
Yokoyama
Akira
A
Arai
Hiroyuki
H
Higuchi
Susumu
S
Kashima
Haruo
H
D000328:Adult; D000368:Aged; D000425:Alcohol Amnestic Disorder / Q000134:cerebrospinal fluid; D000430:Alcohol Withdrawal Delirium / Q000134:cerebrospinal fluid; D000437:Alcoholism / Q000134:cerebrospinal fluid / Q000150:complications; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D008875:Middle Aged; D014899:Wernicke Encephalopathy / Q000134:cerebrospinal fluid* / Q000150:complications; D016875:tau Proteins / Q000134:cerebrospinal fluid*
C054369:MAPT protein, human; D016875:tau Proteins