Human autopsy brain samples were obtained from the New South Wales Tissue Resource Centre at the University of Sydney (http://sydney.edu.au/medicine/pathology/btrc/). Fresh frozen samples of the superior frontal gyrus (Brodmann area 8; referred to as prefrontal cortex (PFC) in this manuscript) were collected from each postmortem sample. Brain tissue was sectioned at 3 mm intervals in the coronal plane. Alcohol-dependent diagnoses were confirmed by physician interviews, review of hospital medical records, questionnaires to next-of-kin, and from pathology, radiology, and neuropsychology reports. Tissue samples were matched as closely as possible according to age, sex, post-mortem interval, pH of tissue, disease classification, and cause of death. To be included as part of the alcohol-dependent cohort, subjects had to meet the following criteria: greater than 18 years of age, no head injury at time of death, lack of developmental disorder, no recent cerebral stroke, no history of other psychiatric or neurological disorders, no history of intravenous or polydrug abuse, negative screen for AIDS and hepatitis B/C, post-mortem interval within 48 h, and diagnosis of AD meeting the DSM-IV criteria1.