Music processing may be preserved in subjects with Alzheimer disease (AD). It is not known which neural substrates are engaged in music processing, and how music familiarity moderates the engagement of these substrates in AD. We investigated fMRI patterns of brain activation during listening to familiar and non-familiar classical music excerpts in subjects with mild to moderate AD and healthy age-matched controls. We related these patterns to behavioral data on familiarity ratings and musical abilities. Five subjects with AD (age M = 76.2, SD = 6.6, MMSE M = 18.6, SD = 7.7, range 9-26) and five healthy controls (age M72.8, SD = 8.0, MMSE M = 29.6, SD =.6, range 29-30) underwent fMRI with a block design paradigm consisting of 75s of familiar music excerpts followed by 30s white noise, vs. 75s of unfamiliar music excerpts. Participants were instructed to just listen. They received a battery of behavioral tests including repeated familiarity ratings of the presented music excerpts (1=very familiar to 5=very unfamiliar), the Montreal Battery for Evaluation of Amusia (MBEA), and the Seashore test of musical abilities. For fMRI a mixed-model 2x2 ANOVA was used to examine effect of group AD vs. controls) and stimulus (familiar vs. unfamiliar) using a p-value <.01 and a minimum cluster size of 200ÂμL. For behavioural data, independent- and paired-sample t-tests were used with p-value <.05. We found a significant group by stimulus effect in fMRI activation patterns. When familiar to unfamiliar music activations were compared, the following regions showed increases in AD and decreases in controls: left/right lingual gyrus, left inferior parietal, left superior, middle and inferior temporal gyri, left precuneus, left culmen, left/right striatum. Ratings for familiar and unfamiliar excerpts did not differ by group (AD M = 1.2, SD =.2 and M = 1.9, SD =.6; Controls M = 1.2, SD =.3, and M = 1.9, SD =.3). Performance on music ability tests also did not differ by group except for Seashore loudness and rhythm (p <.05). Subjects with AD appear to respond more intensely to non-familiar than familiar music by activating regions associated with recognizing familiar patterns and emotions. They do not differ from controls on behavioral measures. This finding suggests differential neural recruitment with respect to preserved music recognition, and its potential application in diagnosis and treatment.