Department of Radiology and Imaging Sciences Works

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Browsing Department of Radiology and Imaging Sciences Works by Author "Abner, Erin L."

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    GWAS of multiple neuropathology endophenotypes identifies new risk loci and provides insights into the genetic risk of dementia
    (Springer Nature, 2024) Shade, Lincoln M. P.; Katsumata, Yuriko; Abner, Erin L.; Aung, Khine Zin; Claas, Steven A.; Qiao, Qi; Aguzzoli Heberle, Bernardo; Brandon, J. Anthony; Page, Madeline L.; Hohman, Timothy J.; Mukherjee, Shubhabrata; Mayeux, Richard P.; Farrer, Lindsay A.; Schellenberg, Gerard D.; Haines, Jonathan L.; Kukull, Walter A.; Nho, Kwangsik; Saykin, Andrew J.; Bennett, David A.; Schneider, Julie A.; National Alzheimer’s Coordinating Center; Ebbert, Mark T. W.; Nelson, Peter T.; Fardo, David W.; Radiology and Imaging Sciences, School of Medicine
    Genome-wide association studies (GWAS) have identified >80 Alzheimer's disease and related dementias (ADRD)-associated genetic loci. However, the clinical outcomes used in most previous studies belie the complex nature of underlying neuropathologies. Here we performed GWAS on 11 ADRD-related neuropathology endophenotypes with participants drawn from the following three sources: the National Alzheimer's Coordinating Center, the Religious Orders Study and Rush Memory and Aging Project, and the Adult Changes in Thought study (n = 7,804 total autopsied participants). We identified eight independent significantly associated loci, of which four were new (COL4A1, PIK3R5, LZTS1 and APOC2). Separately testing known ADRD loci, 19 loci were significantly associated with at least one neuropathology after false-discovery rate adjustment. Genetic colocalization analyses identified pleiotropic effects and quantitative trait loci. Methylation in the cerebral cortex at two sites near APOC2 was associated with cerebral amyloid angiopathy. Studies that include neuropathology endophenotypes are an important step in understanding the mechanisms underlying genetic ADRD risk.
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    Over‐Representation of Extremely Wealthy Neighborhood Social Exposomes for Brain Donors within Alzheimer’s Disease Research Center Brain Banks assessed by the Neighborhoods Study
    (Wiley, 2025-01-09) Kind, Amy J. H.; Bendlin, Barbara B.; Powell, W. Ryan; DeWitt, Amanda; Cheng, Yixuan; Chamberlain, Luke; Sharrow, Jessica; Lyons Boone, Brittney; Abner, Erin L.; Alosco, Michael L.; Apostolova, Liana G.; Bakulski, Kelly M.; Barnes, Lisa L.; Bateman, James R.; Beach, Thomas G.; Bennett, David A.; Brewer, James B.; Carrion, Carmen; Chodosh, Joshua; Craft, Suzanne; Croff, Raina; Fabio, Anthony; Tomaszewski Farias, Sarah; Goldstein, Felicia; Henderson, Victor W.; Karikari, Thomas K.; Kofler, Julia; Kucharska-Newton, Anna M.; Lamar, Melissa; Lanata, Serggio; Lepping, Rebecca J.; Lingler, Jennifer H.; Lockhart, Samuel N.; Mahnken, Jonathan D.; Marsh, Karyn; Meyer, Oanh L.; Miller, Bruce L.; Morris, Jill K.; Neugroschl, Judith A.; O'Connor, Maureen K.; Paulson, Henry L.; Perrin, Richard J.; Pettigrew, Corinne; Pierce, Aimee; Raji, Cyrus A.; Reiman, Eric M.; Risacher, Shannon L.; Rissman, Robert A.; Rodriguez Espinoza, Patricia; Sano, Mary; Saykin, Andrew J.; Serrano, Geidy E.; Soldan, Anja; Sultzer, David L.; Whitmer, Rachel A.; Wisniewski, Thomas; Woltjer, Randall; Zhu, Carolyn W.; Radiology and Imaging Sciences, School of Medicine
    Background: Adverse social exposome (indexed by national Area Deprivation Index [ADI] 80‐100 or ‘high ADI’) is linked to structural inequities and increased risk of Alzheimer’s disease neuropathology. Twenty percent of the US population resides within high ADI areas, predominantly in inner cities, tribal reservations and rural areas. The percentage of brain donors from high ADI areas within the Alzheimer’s Disease Research Center (ADRC) brain bank system is unknown. Objective: Determine ADI for brain donors from 21 ADRC sites as part of the on‐going Neighborhoods Study. Methods: All brain donors in participating ADRC sites with NACC neuropathology data and personal identifiers for ADI linkage (N = 8,637) were included (Figure 1). Geocoded donor addresses were linked to time‐concordant ADI percentiles for year of death. Results: Overall, only 5.6% of ADRC brain donors (N = 488) resided in a high ADI (disadvantaged) neighborhood at death. The remaining donors resided in more advantaged neighborhoods, with nearly 40% of donors living in the wealthiest quintile of neighborhoods, and over 300 brain donors originating from the wealthiest 1% of US neighborhoods (Figure 2). Donors from high ADI (disadvantaged) neighborhoods identified as 87% White (n = 424), 11% Black (55), 1% Multiracial (6) and <1% other/unknown race (3), with 1% Hispanic (5). None identified as American Indian/Alaska Native or Native Hawaiian/Pacific Islander/Asian. In comparison, donors from low ADI neighborhoods were 94% White (n = 7680), 3% Black (273), 1% Multiracial (75), <1% American Indian/Alaska Native (11), <1% Native Hawaiian/Pacific Islander/Asian (60), and <1% other/unknown race (50), with 3% Hispanic (230). Sex distribution was similar (54%, 51% female, respectively). Inclusion of high ADI donors varied dramatically across the 21 ADRC brain banks from a low of 0.6% to high of 20% of all a site’s donors (Figure 3). Conclusions: ADI was determined for over 8,600 brain donors in the ADRC system, demonstrating a marked over‐representation of donors from very low ADI (extremely wealthy) neighborhoods, in addition to site‐to‐site variability. This is the first time a comprehensive cross‐sectional social exposome assessment of this nature has been performed, opening windows for additional mechanistic study of the social exposome on brain pathology. Life course ADI assessments are on‐going.