P1-201 IDENTIFICATION OF HUMAN DISEASE- ASSOCIATEDVARIANTS IN A BRAIN EXPRESSION GENOME-WIDE ASSOCIATION STUDY (EGWAS) Nilufer Ertekin-Taner 1 , Fanggeng Zou 1 , High Seng Chai 2 , Curtis Younkin 1 , Julia Crook 1 , Vernon Pankratz 2 , Mariet Allen 1 , Minerva Carrasquillo 1 , Christopher Rowley 1 , Asha Nair 2 , Sumit Middha 2 , Sooraj Maharjan 2 , Thuy Nguyen 1 , Li Ma 1 , Kimberly Malphrus 1 , Ryan Palusak 1 , Sarah Lincoln 1 , Gina Bisceglio 1 , Constantin Georgescu 1 , Naomi Kouri 1 , Christopher Kolbert 2 , Jin Jen 3 , Ronald Petersen 2 , Neill Graff-Radford 1 , Dennis Dickson 2 , Steven Younkin 1 , 1 Mayo Clinic, Jacksonville, Florida, United States; 2 Mayo Clinic, Rochester, Minnesota, United States. Background: Genetic variants that modify brain gene expression may also influence risk for human diseases. We hypothesize that brain eSNPs are en- riched for genetic variants implicated in human diseases. To determine the contribution of regulatory variants that influence brain gene expression levels (eSNPs) to human central nervous system (CNS) and non-CNS dis- eases, we compared the associations from our eGWAS to the results from the catalog of published human disease/trait GWAS. Results: We identified 2,980 significant cerebellar cis SNP/transcript level associations. Of these, 2,087 were also significant in the temporal cortex. The top 2,980 cis SNPs had 2.4-fold enrichment for human disease associated variants (P <10 -6). We identified novel cis SNP/transcript associations for human disease-associated variants, including CNS diseases such as progressive supranuclear palsy and Parkinson’s disease. We also confirmed known cis SNPs implicated in CNS diseases and others for non-CNS diseases, such as systemic lupus erythematosus and type 1 diabetes mellitus. Conclusions: The significant enrichment of brain cis SNPs amongst disease-associated variants suggests that gene expression changes may be a mechanism of ac- tion for many variants implicated in CNS and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implica- tions. Our findings have implications for the design and interpretation of eG- WAS in general and the use of brain expression quantitative trait loci in the study of human disease genetics. P1-202 BIOCHEMICAL CONSEQUENCES OF TRAUMATIC BRAIN INJURY IN DEMENTIA PUGILISTICA Tyler Kokjohn 1 , Ian Daugs 2 , Chera Maarouf 2 , Ann McKee 3 , Marwan Sabbagh 2 , Thomas Beach 2 , Alex Roher 2 , 1 Midwestern University, Glendale, Arizona, United States; 2 Banner Sun Health Research Institute, Sun City, Arizona, United States; 3 Boston University School of Medicine, Boston, Massachusetts, United States. Background: Dementia pugilistica (DP) comprises an assembly of delete- rious anatomical, biochemical and functional cognitive declines in profes- sional boxers resulting from repetitive blows to the head. The damage is cumulative and permanent with gross structural MRI brain anomalies and chronic traumatic encephalopathy. Ten to twenty percent of cases exhibit more serious neuropsychiatric consequences involving deficiencies in motor skills, behavior and cognition that may end in Alzheimer’s disease (AD) or Parkinson’s disease (PD). Methods: We employed 1D and 2D Western blots and ELISA to quantify 18 protein markers present in the gray matter (GM) and white matter (WM) of 3 elderly individuals (mean: 77 years) who died with dementia and histories of multiple head concussions resulting from professional boxing careers. Case #1 (ApoE E3/3) was neuropathologically uncomplicated, case #2 had the additional diagnosis of AD (ApoE E3/4) and case #3 was complicated with PD (ApoE E3/3). For comparison we utilized a group of 3 age-matched (mean: 75 years) non-demented control (NDC) cases with ApoE E3/3. Results: There were no differences in the Ab levels between DP and NDC cases with the expected exception of case 2 in which Ab42 was significantly elevated. Tau was 60% reduced in the DP vs NDC. Alpha-synuclein was significantly reduced in the DP vs NDC cases. There were qualitative and quantitative differences in the 2D Western blots of tau, 6 -synuclein and GFAP among the DP cases and between DP and NDC. Scanning densitometry demonstrated statistically differences between DP and NDC in neprilysin, BDNF, GFAP, APP, 6 -synuclein, tau in GM and neprilysin, GFAP and MBP in WM. Conclusions: Glial and myelin proteins such as GFAP and MBP were significantly elevated in DP probably in re- sponse to sustained trauma as an effort to maintain the structural integrity of the brain. Boxers also exhibited significant decreases in soluble tau, with extensive isoform differences among themselves and against the NDC group, suggesting extensive levels of insoluble paired helical fila- ments, a feature in DP, probably the result of an attempt to repair neuronal injury. A reduction in BDNF in DP may also reflect a global decay in neuro- protective resources. P1-203 THE IMAGINATION OF FUTURE SCENARIOS IN PATIENTS WITH MILD ALZHEIMER’S DISEASE Yi Lin 1 , Ming-Chyi Pai 2 , 1 National Cheng Kung University, Institute of Behavioral and Medicine, Tainan, Taiwan; 2 National Cheng Kung University Medical Center, Tainan, Taiwan. Background: From the empirical neuroimaging studies, it has been known that the ability to imagine future scenarios, either actual or not, shares a core brain system with the recall of and relies on previous experiences of an in- dividual. Several neuroanatomical substrates of the core system are dam- aged in the early stage of Alzheimer’s disease (AD). The aim of this study was to examine the ability of imagination of future scenarios in mild AD patients. Methods: Participants were patients with very mild (CDR 0.5) and mild AD (CDR 1.0) from an Alzheimer’s Disease Research Center and the age-/sex-matched cognitively healthy controls (HC). Ten pictures of daily activities that older adults usually take in Taiwan were used to elicit imaginations of the future and recalls of the previous experi- ence. The orders of their presentation were counterbalanced. The procedure and scoring were similar to those of the Autobiographical Memory Inter- view (AMI). According to AMI scoring system, we categorized the contents of transcripts into internal episodic and external semantic components. Us- ing a repeated factorial ANOVA. Results: Thirteen AD patients (8 males, mean age 73, education 11 years, MMSE 22, CASI 75) and 11 HC (2 males, mean age 70, education 9 years, MMSE 28, CASI 92) completed the study. No difference was detected between two groups in basic visual perceptual and verbal fluency listening comprehension abilities, while AD had a poorer semantic verbal fluency. For both AD and HC, the performance in recall tri- als was better than that in imagination trials, F(1, 22) ¼ 14.28, P ¼ .001. AD patients exhibited less internal episodic details (mean ¼ 8.39, SD ¼ 1.15) as compared with HC (mean ¼ 16.36, SD ¼ 1.65), in particular for the imag- ination trials. Moreover, an interaction of details and groups was detected, F(1, 22) ¼ 26.59, P ¼ .000; AD had more external semantic details while HC had more internal episodic details. Conclusions: Compared to HC, mild AD produced more external semantic details in remembering past events and in imaging future events, while exhibited a significant reduction in the internal episodic details of imagination. This finding demonstrates an- other cognitive deficit in early AD patients and also sheds a light on the un- derstanding of the human memory. P1-204 RELATED DEMENTIAS Yulia Surova 1 , Malin Wennstr€ om 2 , Fredrik Bostrom 2 , Christer Nilsson 3 , Lennart Minthon 2 , Oskar Hansson 4 , Henrietta Nielsen 2 , 1 Lund University, Department of Clinical Sciences Lund, Neurology Clinic, Lund, Sweden; 2 Lund University, Malm€ o, Sweden; 3 Lund University, Lund, Sweden; 4 Neuropsychiatric Clinic, Malm€ o, Sweden. Background: Inflammatory processes are strongly related to neurodegen- erative processes, which is well-established in Alzheimer’s disease (AD). However, studies evaluating cerebrospinal fluid (CSF) levels of chemo- kines including interleukin (IL)-8, interferon gamma-induced protein-10 Poster Presentations: P1 P178