o145-6008/99/2304-0515$03.0010 zyxwvutsrqp Au OH01 I5M: CLINICAL AND EXPERIMENTAL RESEARCH Vol. 23, No. 4 z April 1999 Cerebrospinal Fluid Tau Protein Levels in Demented and Nondemented Alcoholics Yu-ichi Morikawa, Hiroyuki Arai, Sachio Matsushita, Motoichiro Kato, Susumu Higuchi, Masakazu Miura, Hisako Kawakami, Makoto Higuchi, Nobuyuki Okamura, Manabu Tashiro, Toshifumi Matsui, and Hidetada Sasaki The tau protein levels in cerebrospinal fluid (CSF-tau) were examined in 27 patients with alcohol dependence (20 demented and 7 nondemented), 36 age and dementia severity-matched patients with Alzheimer’s disease (AD), and 23 age-matched normal control subjects. The CSF-tau levels in the de- mented alcoholic group (alcohol-induced organic brain disorders, 25.4 zyxwvu -t 10.2pgiml) was significantly lower (p < 0.0001) than that in the AD group (96.1 zyxwvutsr 2 53.3 pgiml), but not significantly different from that in the nondemented alcoholics (18.1 -t 10.2 pgirnl) or the controls (19.2 -t 12.9 pgiml). Using a 44.9 pgiml as a cut-off value (mean + 2 SD of the normal control group), only one patient with alcohol-induced organic brain disorders exceeded the value, whereas 3 of 36 of the AD group showed CSF-tau levels less than this level. These findings suggest that alcohol-induced organic brain disorders are a group of dementias that are characterized by normal CSF-tau levels, and that the CSF examination for tau in combination with other clinical findings may help in differentiating alcohol-induced organic brain disorders from AD. Key Words: Alcohol-Induced Organic Brain Disorders, Alzheimer’s Disease, Cerebrospinal Fluid, Tau Protein, Differential Diagnosis. ECENT STUDIES demonstrate that heavy alcohol use zyxwv R is a major contributing factor to the emergence of dementia in more than 20% of patients diagnosed as having Chronic alcohol dependence may result in central (CNS) and peripheral nervous system damage, leading to a variety of neuropsychiatric disorders including Wernicke’s encephalopathy, Korsakoff‘s psychosis, and de- mentia. There is increasing evidence to suggest that such an alcoholic brain damage results from a combination of met- abolic and toxic insults including the direct effect of alco- hol/acetaldehyde, the effects of thiamine deficiency and the effects of gastrointestinal and liver disease^.^ It is possible that elderly alcohol-drinkers with a long and habitual use of alcohol until the age of 60s or 70s are likely to develop such alcoholic brain damage. Indeed, ventricular and sulcal ce- rebrospinal fluid (CSF) volumes in older alcoholics were reported to be greater than would be expected for their age, suggesting greater vulnerability of the aging brain to alco- h01.~ Furthermore, because the prevalence of Alzheimer’s From the Department of Geriatric Medicine, Tohoku University School of Medicine (Y.M., HA., M.H., N.O., M.T., T.M., H.S.), Sendai, Miyagi 980; Department of PJychiatry (S.M., S.H.), Kurihama National Hospital, Na- tional Institute on Alcoholism, Kanagawa 239; Department of Neuropsychi- atry (M.K.), Tokyo Dental College, Ichikawa General Hospital, Chiba 272; and Research and Development Department (M.M., H.K), Mitsubishi zyxwvutsr Ka- gaku Bio-clinical Laboratories, Tokyo 114, Japan. Received for publication September 30, 1998; accepted December 14, 1998. Reprints requests: Hiroyuki Arai, M.D., Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan; Fax: 022-71 7- 7186; E-mail: h-ara @mail.cc.tohoku.ac.jp Copyright zyxwvutsrqp 0 1999 by the Research Society on Alcoholism. Alcohol Clin Erp Res, Vol23, No 4, 1999: pp 515-511 disease (AD) increaseswith age, the likelihood of coexistence of AD and alcohol-induced dementia would be expected to occur in elderly alcohol drinkers. In fact, a prolonged history of excessive alcohol intake often accompanies patients whose clinical features are otherwise consistent with AD. Recent studies of CSF levels of neurotransmitters and/or their metabolites5 as well as CSF acetylcholinesterase activity6 in alcoholic patients are intriguing. However, it should be determined which of these or other molecules will reflect fundamental features of alcohol-induced brain damage. A series of recent studies have concluded that cerebro- spinal fluid tau (CSF-tau) protein levels were significantly increased in patients with AD compared to other neuro- logical diseases and normal control subjects (see Ref. 7 and citations therein). The microtubule-associated protein tau is abnormally phosphorylated and converted into paired helical filaments that accumulate in dystrophic neurites and neurofibrillary tangles within affected AD CNS neurons.8 Therefore, it is hypothesized that the increase in the CSF- tau levels in AD might reflect a massive and progressive death of specific population of vulnerable neurons, and it can be used as a reliable biochemical marker to aid in the diagnosis of AD. Because dementia associated with alcohol dependence might have a better prognosis compared with AD and it can be potentially preventable and/or treatable by social, medical, and rehabilitation therapy, in contrast to less treatable situation in AD at the present time, it is important to be able to separate alcohol-induced organic brain disorders from AD with more accuracy and consis- tency. Our study was therefore undertaken to address the question of whether measurements of CSF-tau levels can 575