Jennifer Eastman

Common variants in ABCA7 and MS4A6A are associated with cortical and hippocampal atrophy

The precise physiologic function of many of the recently discovered Alzheimers disease risk variants remains unknown. The downstream effects of genetic variants remain largely unexplored. We studied the relationship between the top 10 non-APOE genes with cortical and hippocampal atrophy as markers of neurodegeneration using 1.5T magnetic resonance imaging, 1-million single nucleotide polymorphism Illumina Human Omni-Quad array and Illumina Human BeadChip peripheral blood expression array data on 50 cognitively normal and 98 mild cognitive impairment subjects. After explicit matching of cortical and hippocampal morphology, we computed in 3D, the cortical thickness and hippocampal radial distance measures for each participant. Associations between the top 10 non-APOE genome-wide hits and neurodegeneration were explored using linear regression. Map-wise statistical significance was determined with permutations using threshold of p < 0.01. MS4A6A rs610932 and ABCA7 rs3764650 demonstrated significant associations with cortical and hippocampal atrophy. Exploratory MS4A6A and ABCA7 peripheral blood expression analyses revealed a similar pattern of associations with cortical neurodegeneration. To our knowledge, this is the first report of the effect of ABCA7 and MS4A6A on neurodegeneration.

Novel verbal fluency scores and structural brain imaging for prediction of cognitive outcome in mild cognitive impairment

The objective of this study was to assess the utility of novel verbal fluency scores for predicting conversion from mild cognitive impairment (MCI) to clinical Alzheimers disease (AD).

Plasma BDNF levels associate with Pittsburgh Compound B binding in the brain

Brain‐derived neurotrophic factor (BDNF) plays an important role in Alzheimers disease (AD) and other neurodegenerative disorders. BDNF function is adversely affected by amyloid beta in AD. BDNF levels in brain and peripheral tissues are lower in patients with AD and mild cognitive impairment (MCI) than in controls. Here we examined the association between plasma levels of BDNF and amyloid deposition in the brain measured with Pittsburgh Compound B (PiB).

Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding

Objective: We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association. Methods: Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimers Disease Neuroimaging Initiative 1 (ADNI1) participants with available [11C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes. Results: Low plasma apoE was significantly associated with high PiB SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A. Conclusions: Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction.

Caudate volume change in primary progressive aphasia with motor speech symptoms

magnetic resonance imaging (fMRI) to assess the PFC-involved neural connections. Results:As expected, we found greater IIVRT in the MCI group compared to HCs. In the MCI group, IIVRT was positively correlated with the degree of connectivity in the fronto-basal ganglia circuit, and negatively correlated with the ECN in the right hemisphere. Conversely, IIVRT was negatively correlated with connectivity in fronto-basal ganglia circuit, and had no correlation with the ECN in the HC group. Conclusions: The altered relationship between IIVRT and two PFC-involved neural connections in MCI may indicate an early marker of the neurodegenerative process, though further work determining the causal link is needed.

AD RISK GENE MINOR ALLELES MODULATE RELATIONSHIP BETWEEN PLASMA APOE AND PIB BINDING IN THE BRAIN

IC-P-090 AD RISK GENE MINOR ALLELES MODULATE RELATIONSHIP BETWEEN PLASMA APOE AND PIB BINDING IN THE BRAIN Andreas Lazaris, Andreas Lazaris, Kristy Hwang, Jennifer Ann Eastman, Paul Thompson, Karen Gylys, Greg M. Cole, Liana Apostolova, Sophie Sokolow, UC Berkeley, Berkeley, California, United States; UCLA, Los Angeles, California, United States; University of California Los Angeles, Los Angeles, California, United States; USC, Los Angeles, California, United States; UCLA School of Nursing, Los Angeles, California, United States. Contact e-mail: alazaris@berkeley.edu