Neuroscience Letters 400 (2006) 97–100 Autotaxin expression is enhanced in frontal cortex of Alzheimer-type dementia patients  Ken Umemura a,1 , Nobuyuki Yamashita a,2 , Xiaonian Yu a , Kunimasa Arima b , Takashi Asada c , Takao Makifuchi d , Shigeo Murayama e , Yuko Saito e , Kazutomi Kanamaru e , Yuichi Goto a , Shinichi Kohsaka a , Ichiro Kanazawa a,b , Hideo Kimura a,∗ a National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan b National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan c Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan d National Saigata Hospital, Saigata, Japan e Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan Received 11 January 2006; received in revised form 3 February 2006; accepted 6 February 2006 Abstract We searched for genes differentially expressed in the frontal cortices of Alzheimer-type dementia (ATD) patients compared with those of non- ATD controls using DNA microarray and quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses. Here we show that the expression level of the autotaxin (also called lysophospholipase D or ecto-nucleotide pyrophosphatase/phosphodiesterase 2) gene was significantly greater in ATD cortices than in non-ATD cortices. In both ATD and non-ATD groups, the expression levels were greater in patients with the apoE 3/4 genotype than in patients with the apoE 3/3 genotype, although the differences were not statistically significant. These observations suggest that expression of the autotaxin gene and cell signaling by lysophosphatidic acid may be involved in the pathology of ATD, and that this cell signaling pathway may be a potential target of treatments for ATD. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Alzheimer-type dementia; Microarray; Autotaxin; Brain The frontal cortex has major roles in higher cognitive functions, and disintegration of cognition is a major behavioral symptom of Alzheimer-type dementia (ATD) as well as memory disturbance [3]. Severe atrophy is sometimes observed in the frontal cortex as well as other sites including the hippocampus and parahip- pocampal gyrus of ATD patients. Genetic linkage studies of late-onset familial Alzheimer’s disease (AD) showed that AD-susceptibility is linked to the  Supplementary material: A list of the age, gender, diagnosis for Alzheimer- type dementia, apo E genotype, and logarithmic value for the relative expres- sion level of the autotoxin gene in each subject belonging to specimen sets C and D, normalized to that of the -actin gene, determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) experiments (Excel document). ∗ Corresponding author. Tel.: +81 42 346 1725; fax: +81 42 346 1755. E-mail address: kimura@ncnp.go.jp (H. Kimura). 1 Present address: Gifu International Institute of Biotechnology Foundation, Kakamigahara, Gifu, Japan. 2 Present address: Meiji Seika Kaisha Ltd., Yokohama, Kanagawa, Japan. apolipoprotein E (ApoE) gene located on chromosome 19 [7]. Amyloid deposits co-localize with Apo E [6] and amyloid - protein binds to ApoE. The Apo E gene has three variants, 2, 3, and 4, and 3 is the most common allele. The frequency of the 4 allele is higher in AD patients [8], and the copy number of this allele correlates with the age of onset of AD [1]. How- ever, the sensitivity of ATD diagnosis using only this allele as a marker was no more than 65% [4]. The present study shows that autotaxin gene expression is greatly enhanced in the brains of ATD-patients compared with those of normal individuals. Expression of this gene tends to be greater in patients with apoE 3/4 than in those with apoE 3/3. We tested postmortem brains listed in Table 1. Specimen sets A, B, and C were obtained from the National Center of Neurology and Psychiatry (NCNP; Kodaira, Tokyo, Japan) and National Saigata Hospital (Oogatamachi, Niigata, Japan). Spec- imen set D was from The Tokyo Metropolitan Institute of Geron- tology (Itabashi, Tokyo, Japan). The patients in the non-ATD group of set D did not have amyotrophic lateral sclerosis or 0304-3940/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2006.02.008