Poster Presentations P3: P3-282
APOLIPOPROTEIN E4 ALLELE AND GREY MATTER ATROPHY IN FRONTOTEMPORAL DEMENTIA AND ALZHEIMER’S DISEASE: A DISEASE-SPECIFIC REGIONAL EFFECT 1
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Keith A. Vossel , Federica Agosta , Anna M. Karydas , Adam L. Boxer1, Stephen J. Bonasera1, Bruce L. Miller1, Maria L. Gorno-Tempini1, 1Memory and Aging Center, Department of Neurology, UCSF, San Francisco, CA, USA; 2Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Milan, Italy. Contact e-mail:
[email protected] Background: The Apolipoprotein E (ApoE) ⑀4 allele is strongly linked with Alzheimer’s disease (AD) but is also becoming recognized as disease modifier in other neurological disorders. The effect of the ApoE ⑀4 allele on brain atrophy in frontotemporal dementia (FTD) has not been clarified. Objective: In this study, we compare the effect of ApoE ⑀4 allele on the pattern of gray matter (GM) atrophy in behavioral variant FTD and AD at presentation. Methods: T1-weighted images (1.5T) were obtained from 32 patients who met Neary criteria for behavioral variant FTD (mean age 59 years, median Clinical Dementia Rating [CDR] 1.0), 56 patients with NINCDS-ADRDA probable AD (mean age 66 years, median CDR 1.0), and 62 healthy controls (mean age 65 years) at presentation. ApoE genotyping was obtained by standard sequencing. Voxel-based morphometry using Statistical Parametric Mapping (SPM5) measured GM density in patients who possessed at least one ApoE ⑀4 allele compared to controls and non-carriers in each patient’s group. Age, gender, total intracranial volume, and disease severity were included in the statistical analysis as nuisance parameters. Results: ApoE ⑀4 allele carriers were 8 (25%) within the FTD group, 30 (53.6%) within the AD group, and 12 (19.3%) within controls. There was no difference in age, gender, or disease severity between carriers and non-carriers in each group. Compared to controls and FTD noncarriers, FTD patients carrying ⑀4 allele showed greater atrophy in a large area including medial and dorsolateral frontal cortex and anterior insula bilaterally. When compared to controls and AD non-carriers, AD patients carrying ⑀4 showed greater atrophy in the left hippocampus and precuneus, and in the bilateral parietal cortex.
P3-283
T605 FAMILIAL EARLY-ONSET LEWY BODY DEMENTIA: CLINICAL, PATHOLOGICAL AND GENETIC DISSECTION
Alberto Lleo1, Isidre Ferrer2, Laura Molina1, Luis Barraquer-Bordas1, Cristina Guardia1, Ana Gonzalez-Neira3, Rafael Blesa1, Teresa Go´mez-Isla1, Carles Roig1, Jordi Clarimon1, 1Hospital Sant Pau, Barcelona, Spain; 2Hospital de Bellvitge, Hospitalet de Llobregat, Spain; 3Centro Nacional de Genotipado (CEGEN), Madrid, Spain. Contact e-mail:
[email protected] Background: Familial ocurrence of early-onset Lewy-body dementia is very infrequent and only a few families have been reported. Methods: We describe the clinical, pathological and genetic findings of four individuals from a two-generation family with early-onset autosonal dominant Lewybody dementia. Mutation screening was performed for alpha- and betasinuclein, presenilin 1 and 2, amyloid precursor protein (APP) and MAPT using direct sequencing. Genome wide single nucleotide polymorphism typing using Ilumina’s Human Hap550 Genotyping BeadChip was also performed. Results: Three siblings presented with a clinical picture of cognitive impairment, parkinsonism and visual hallucinations with an age at onset between 26 and 29 years. Neuropathological examination disclosed abundant Lewy bodies and Lewy neurites in basal ganglia and the neocortex reactive for both alpha-sinuclein and tau. No amyloid plaques were detected. The father developed cognitive impairment, with early spontaneous parkinsonism at the age of 77. DAT scan showed low dopamine transporter uptake in the gasal ganglia. Genetic analysis showed no mutations in the alpha- or beta-synuclein, MAPT, APP, presenilin 1 or 2 genes. No structural genomic alterations (deletions and duplications) were found except for some described polymorphic copy number variations of the human genome. Conclusions: We report a family with pathologicalconfirmed early-onset Lewy-body dementia with coexistence of both tau and synuclein in the same inclusions. The absence of structural mutations in the genome and the lack of point mutations in genes known to cause LBD suggests that a novel locus or loci are involved in this neurodegenerative disease. P3-284
THE UBQLN1 POLYMORPHISM AND COGNITIVE IMPAIRMENT. RESULTS FROM THE DETCOGEN STUDY
Manuel Ferna´ndez1, Xabier Elcoroaristizabal Martı´n2, Maria de los Angeles Martinez de Pancorbo3, Luis Galdos4, Jessica Castro1, JM Uterga5, B. Indakoetxea6, M. Gomez7, J. Morazar8, N. Ortiz5, M. Barandiaran6, Ana Molano1, R. Bereincua1, MC Gonzalez Ferna´ndez3, S. Ingle´s4, M. Carrasco7, 1Hospital de Cruces, Baracaldo, Spain; 2Servicio General de Investigacion Geno´mica: Banco de ADN, Universidad del Paı´s Vasco UPV/EHU, Vitoria-Gasteiz, Spain; 3Servicio General de Investigacio´n Geno´mica: Banco de ADN. Universidad del Paı´s Vasco UPV/EHU., Vitoria-Gasteiz, Spain; 4Hospital de Txagorritxu, Vitoria-Gasteiz, Spain; 5Hospital de Basurto, Bilbao, Spain; 6Hospital de Donosti, San Sebastian, Spain; 7 Hospital de Galdakao, Galdakao, Spain; 8Hospital de Santiago Apostol, Vitoria-Gasteiz, Spain. Contact e-mail:
[email protected]
Conclusions: Our study showed that ApoE ⑀4 is associated with a more severe pattern of GM atrophy in disease-specific regions in patients with both behavioral variant FTD and AD at presentation. This anteriorto-posterior dissociation of ApoE ⑀4 effect suggests that ⑀4 may alter the morphologic expression of neurodegenerative disease within vulnerable neural networks.
Background: Genetic, metabolic and enviromental factors play a role in Alzheimer’s disease (AD). In recent years, a number of genes including UBQLN1, have been identified as possible new risk factor for AD. UBQLN1 is a possible candidate gene because of its role in proteasomal degradation and its interaction with presenilin 1 (PS1) and presenilin 2 (PS2). Methods: A total of 146 healthy controls, 78 AD and 77 MCI-AT patients recruited from neurology departments in Basque Country (Spain). Clinical criteria for dementia and AD (DSM IV and NINCDS-ADRDA) and Petersen’s criteria for MCI-AT were used, a broad battery of neuropsychological tests were used to establish diagnostic groups. The DNA bank at Basque Country University (UPV-EHU) determined the APOE genotypes by polymerase chain reaction (PCR) and RFLPs. UBQLN1 was
