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ɛ3 Genotype
e16
Hot Topics TOMM40 group had significantly less gray matter volume in the ventral posterior cingulate and precuneus, a region of the brain affected early in LOAD. Conclusions: To our knowledge, this is the first study to associate TOMM40 523 genotypes to brain imaging in people at risk for AD. These findings suggest that the group with very long TOMM40 poly-T lengths may be experiencing incipient LOAD-related cognitive and brain changes. The participants in this study are being followed over time to determine genetic and other factors that predict cognitive decline and dementia.
Figure 1. Statistical parametric maps (SPMs) showing higher PiB retention in NL with AD-mothers compared to controls (top two rows) and to NL with AD-fathers (middle two rows), and in NL with AD-fathers compared to controls (bottom two rows). Areas of increased PiB retention are represented on a red-to-yellow color-coded scale, reflecting P values between 0.01-0.001, as indicated on the right side of figure. SPMs are displayed onto the axial and sagittal views of a standard, spatially normalized MRI.
Figure 2. Statistical parametric maps (SPMs) showing reduced glucose metabolism in NL with AD-mothers compared to controls (top two rows) and to NL with AD-fathers (bottom two rows). Areas of reduced metabolism are represented on a blue-to-yellow color-coded scale, reflecting P values between 0.01-0.001, as indicated on the right side of figure. SPMs are displayed onto the axial and sagittal views of a standard, spatially normalized MRI.
O4-03-04
TOMM40 IS ASSOCIATED WITH GRAY MATTER VOLUME IN MIDDLE-AGED PERSONS WITH APOE 33/33 GENOTYPE
Sterling C. Johnson1,2, Asenath La Rue1, Bruce P. Hermann1, Guofan Xu1, Rebecca L. Koscik1, Erin M. Jonaitas1, Barbara B. Bendlin1,2, Allen D. Roses3, Ann M. Saunders3, Michael W. Lutz3, Sanjay Asthana1,2, Robert C. Green4, Mark A. Sager1, 1University of Wisconsin, Madison, WI, USA; 2William S. Middleton Veterans Hospital, Madison, WI, USA; 3Duke University, Durham, NC, USA; 4Boston University, Boston, MA, USA. Background: Apolipoprotein E (APOE) genotypes are associated with variable risk of developing late onset Alzheimer’s disease (LOAD), with APOE 34 having higher risk. A variable poly-T length polymorphism at rs10524523, within intron 6 of the TOMM40 gene has very recently been shown to influence age of onset in LOAD, where very long poly-T length was associated with earlier disease onset, and short poly-T length associated with later onset. In this study, we tested the hypothesis that brain changes antedating symptomatic LOAD may be associated with this TOMM40 polymorphism. Methods: Among healthy APOE 33 homozygous adults (mean age 57), we compared those homozygous for very long (VL/VL; n ¼ 33) TOMM40 poly-T lengths (who are presumably at higher risk) to those homozygous for short (S/S; n ¼ 37) poly-T lengths on structural brain imaging. Voxel-based morphometry was used to assess gray matter volume using the software SPM8. Gray matter probability maps were entered into a voxel-wise ANCOVA where Age and Intracranial volume were covariates Results: Results were that the VL/VL
O4-03-05
AMYLOID AND TAU PROTEINS IN CORTICAL BRAIN BIOPSY AND ALZHEIMER’S DISEASE
Ville Leinonen1, Anne M. Koivisto1,2, Sakari Savolainen1, Jaana Rummukainen1, Okko T. Pyykko¨1, Mikael Fraunberg1, Juha E. Ja¨a¨skela¨inen1, Hilkka Soininen1,2, Irina Alafuzoff2,3, 1Kuopio University Hospital, Kuopio, Finland; 2University of Eastern Finland, Kuopio, Finland; 3University of Uppsala, Uppsala, Sweden.
Hot Topics TOMM40 group had significantly less gray matter volume in the ventral posterior cingulate and precuneus, a region of the brain affected early in LOAD. Conclusions: To our knowledge, this is the first study to associate TOMM40 523 genotypes to brain imaging in people at risk for AD. These findings suggest that the group with very long TOMM40 poly-T lengths may be experiencing incipient LOAD-related cognitive and brain changes. The participants in this study are being followed over time to determine genetic and other factors that predict cognitive decline and dementia.
Figure 1. Statistical parametric maps (SPMs) showing higher PiB retention in NL with AD-mothers compared to controls (top two rows) and to NL with AD-fathers (middle two rows), and in NL with AD-fathers compared to controls (bottom two rows). Areas of increased PiB retention are represented on a red-to-yellow color-coded scale, reflecting P values between 0.01-0.001, as indicated on the right side of figure. SPMs are displayed onto the axial and sagittal views of a standard, spatially normalized MRI.
Figure 2. Statistical parametric maps (SPMs) showing reduced glucose metabolism in NL with AD-mothers compared to controls (top two rows) and to NL with AD-fathers (bottom two rows). Areas of reduced metabolism are represented on a blue-to-yellow color-coded scale, reflecting P values between 0.01-0.001, as indicated on the right side of figure. SPMs are displayed onto the axial and sagittal views of a standard, spatially normalized MRI.
O4-03-04
TOMM40 IS ASSOCIATED WITH GRAY MATTER VOLUME IN MIDDLE-AGED PERSONS WITH APOE 33/33 GENOTYPE
Sterling C. Johnson1,2, Asenath La Rue1, Bruce P. Hermann1, Guofan Xu1, Rebecca L. Koscik1, Erin M. Jonaitas1, Barbara B. Bendlin1,2, Allen D. Roses3, Ann M. Saunders3, Michael W. Lutz3, Sanjay Asthana1,2, Robert C. Green4, Mark A. Sager1, 1University of Wisconsin, Madison, WI, USA; 2William S. Middleton Veterans Hospital, Madison, WI, USA; 3Duke University, Durham, NC, USA; 4Boston University, Boston, MA, USA. Background: Apolipoprotein E (APOE) genotypes are associated with variable risk of developing late onset Alzheimer’s disease (LOAD), with APOE 34 having higher risk. A variable poly-T length polymorphism at rs10524523, within intron 6 of the TOMM40 gene has very recently been shown to influence age of onset in LOAD, where very long poly-T length was associated with earlier disease onset, and short poly-T length associated with later onset. In this study, we tested the hypothesis that brain changes antedating symptomatic LOAD may be associated with this TOMM40 polymorphism. Methods: Among healthy APOE 33 homozygous adults (mean age 57), we compared those homozygous for very long (VL/VL; n ¼ 33) TOMM40 poly-T lengths (who are presumably at higher risk) to those homozygous for short (S/S; n ¼ 37) poly-T lengths on structural brain imaging. Voxel-based morphometry was used to assess gray matter volume using the software SPM8. Gray matter probability maps were entered into a voxel-wise ANCOVA where Age and Intracranial volume were covariates Results: Results were that the VL/VL
O4-03-05
AMYLOID AND TAU PROTEINS IN CORTICAL BRAIN BIOPSY AND ALZHEIMER’S DISEASE
Ville Leinonen1, Anne M. Koivisto1,2, Sakari Savolainen1, Jaana Rummukainen1, Okko T. Pyykko¨1, Mikael Fraunberg1, Juha E. Ja¨a¨skela¨inen1, Hilkka Soininen1,2, Irina Alafuzoff2,3, 1Kuopio University Hospital, Kuopio, Finland; 2University of Eastern Finland, Kuopio, Finland; 3University of Uppsala, Uppsala, Sweden.