Background: Biotin and pantothenic acid deficiences are thought to be rare conditions. Elevated levels of pantothenic acid, a water-soluble vita- min, have not been reported in the medical literature. These vitamins are essential for energy metabolism and acetylcholine production. More than 50 patients in our memory clinic have been identified with biotin defi- ciency. Half of these patients have elevated pantothenic acid levels and a third have a pantothenic acid deficiency. Changes in the globus pallidus interna (GPi) on magnetic resonance imaging (MRI) have been identified which appear to correlate with biotin deficiency and dementia. Methods: Serum levels of biotin and pantothenic acid were obtained on 54 patients being evaluated in a community-based memory clinic when they presented with a dementia and T2-weighted MRI images revealed hypointensity in the GPi with or without an area of central hyperintensity. Hippocampal atrophy was estimated by the author using coronal MRI images at the level of the mammillary bodies. Results: Abnormal serum biotin levels were identified in 96.3% of patients with dementia and hypointensity of the GPi on T2-weighted MRI; 50 patients (92.6%) had a biotin deficiency (200 pg/ml) and 74% had biotin levels 100 pg/ml. Pantothenic acid levels were normal in ten patients (normal range 200-1800 ng/ml), elevated in 50% of patients (range 2081-28,597 ng/ml) and low in 31.5% of patients. Hippocampal atrophy was absent or mild in 45/54 cases (83%). An area of central hyperintensity within the GPi hypointensity is seen in 39/54 cases (72%). Conclusions: Biotin deficiency and abnormal levels of pantothenic acid are extremely common in this cohort of patients with dementia and hy- pointensity of the GPi on T2-weighted MR images. Three quarters of these patients have biotin levels below the sensitivity limit of the test (100 pg/ml) and a quarter have pantothenic acid levels 3 times the upper limit of normal, a finding not previously reported in the medical literature. Biotin and pantothenic acid are carried across cell membranes by the sodium- dependent multivitamin transporter (SMVT). These findings implicate dys- regulation of the SMVT in a dementia exhibiting changes within the GPi and without the hippocampal atrophy commonly seen in Alzheimer’s disease. P3-401 VALIDATION OF A TRPM3-SPECIFIC ANTIBODY AND TRMP3 EXPRESSION IN MOUSE BRAIN Jamie L. Crispino, Jacob N. Marcus, Heike Hering, Merck Research Labs, Boston, MA, USA. Contact e-mail: jamie_crispino@merck.com Background: Alzheimer’s disease is characterized by accumulation of amyloid beta-peptide (Abeta) in specific regions of the brain. Abeta is generated through proteolytic processing of the amyloid precursor protein (APP). Increased levels of Abeta can cause disruption in cellular calcium homeostasis thereby making neurons vulnerable to excitotoxicity and ap- optosis. Conversely, disruption in calcium signaling can directly affect APP processing and Abeta formation. There is increasing evidence that TRP (transient receptor potential) channels play a role in neuronal calcium signaling and a disruption of TRP channels can lead to intracellular cal- cium dyshomeostasis. Methods: To investigate if TRPM3 is potentially involved Alzheimer’s disease pathology we generated antibodies specific for mouse TRPM3. Results: Here we describe the characterization of these antibodies and the expression pattern of TRPM3 protein in mouse brain. Microarray data from human tissue suggested that TRPM3 is highly ex- pressed in several regions of the brain and retina. Consistently, we found TRPM3 protein to be highly expressed in human retina. In mouse brain, the highest expression of TRPM3 was found in the CA1 region of the hip- pocampus, the lateral septum, and the hypothalamus. In primary hippocam- pal neurons, TRPM3 was expressed throughout the somatodendritic and axonal compartment. Conclusions: In conclusion, our data suggest that TRPM3 is localized in brain regions affected in Alzheimer’s disease. P3-402 AGE-RELATED LOSS OF CALBINDIN IDENTIFIES BASAL FOREBRAIN CHOLINERGIC NEURONS DESTINED TO DEGENERATE IN ALZHEIMER’S DISEASE Dianne de Leon, Alaina Baker, Chuang-Kuo Wu, Jing Bu, Changiz Geula, Northwestern University, Chicago, IL, USA. Contact e-mail: dianne@u.northwestern.edu Background: The reasons for the vulnerability of select neuronal popula- tions in Alzheimer’s Disease (AD) remain unknown. We have used the basal forebrain cholinergic neurons (BFCN), which are vulnerable to de- generation early in the course of AD, to determine of the causes of selective neuronal vulnerability. We have observed a selective loss of the calcium binding protein calbindin-D28K from the human BFCN in the course of normal aging. The calcium dysregulation caused by the loss of calbindin may contribute to the loss of BFCN in AD. In the present set of experi- ments, we investigated whether the BFCN which degenerate in AD are those which lose calbindin in the course of aging. Methods: Immunohis- tochemical methods were used in postmortem brains from young (65 years), old and AD cases. Cell counting techniques were used to determine the numbers of immunoreactive neurons. Results: The number of choline acetyltransferase (ChAT) and low affinity neurotrophin receptor (p75NTR) immunoreactive BFCN remained constant in old individuals when com- pared with the young and displayed a significant decrease in AD. In contrast, the number of calbindin-positive BFCN showed a significant decrease in normal aged individuals when compared with the young and remained constant in AD. The percentage of calbindin-positive BFCN in the aged was significantly lower when compared with the young. Of great interest, the percentage of the remaining BFCN in AD which contained calbindin immunoreactivity displayed a significant increase when com- pared with the normal aged, indicating that the majority of surviving BFCN in AD are calbindin-positive. Western blot analysis showed no increase in the total levels of calbinidin protein in AD basal forebrain, suggesting that the maintained calbindin immunoreactivity in AD BFCN is not due to reactive upregulation. Conclusions: These observations indicate that the loss of cholinergic neurons in AD occurs preferentially in the BFCN which lose their calbindin in the course of normal aging and that the BFCN which contain calbindin survive the neurodegenerative process. It is likely that loss of calbindin during aging deprives the BFCN from the calcium buffering capacity of this protein, leaving them vulnerable to degeneration due to calcium toxicity in AD. P3-403 PARKIN UBIQUITYLATES PHOSPHOLIPASE C-1 AND PROTECTS AGAINST DOPAMINE INDUCED CELL DEATH Nodi Dehvari 1 , Anna Sandebring 1 , Amilcar Flores-Morales 1 , Laura Mateos 1 , Elena Karpilovski 1 , Mark R. Cookson 2 , Matthew S. Goldberg 3 , Richard F. Cowburn 4 , Angel Cedazo-Minguez 1 , 1 Karolinska Institutet, Stockholm, Sweden; 2 National Institutes of Health, Bethesda, MD, USA; 3 The University of Texas Southwestern Medical Center, Dallas, TX, USA; 4 AstraZeneca R&D, So ¨derta ¨lje, Sweden. Contact e-mail: nodi.dehvari@ki.se Background: Parkin is an E3 ubiquitin ligase in which mutations cause early onset autosomal recessive juvenile Parkinsonism (ARJP). ARJP is characterized by an early disease onset (before the age of 40) and by the T639 Poster Presentations P3: