Browsing by Author "Paulson, Henry L."

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    Adverse Social Exposome by Area Deprivation Index (ADI) and Alzheimer’s Disease and Related Dementias (ADRD) Neuropathology for a National Cohort of Brain Donors within the Neighborhoods Study
    (Wiley, 2025-01-09) Kind, Amy J. H.; Bendlin, Barbara B.; Keller, Sarah A.; Powell, W. Ryan; DeWitt, Amanda; Cheng, Yixuan; Chamberlain, Luke; Lyons Boone, Brittney; Miller, Megan J.; Vik, Stacie M.; 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; 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.; 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.; Sultzer, David L.; Whitmer, Rachel A.; Wisniewski, Thomas; Woltjer, Randall; Zhu, Carolyn W.; Neurology, School of Medicine
    Background: Adverse social exposome (indexed by high national Area Deprivation Index [ADI]) is linked to structural inequities and increased risk of clinical dementia diagnosis, yet linkage to ADRD neuropathology remains largely unknown. Early work from single site brain banks suggests a relationship, but assessment in large national cohorts is needed to increase generalizability and depth, particularly for rarer neuropathology findings. Objective: Determine the association between adverse social exposome by ADI and ADRD neuropathology for brain donors from 21 Alzheimer’s Disease Research Center (ADRC) brain banks as part of the on‐going Neighborhoods Study. Methods: All brain donors in participating sites with neuropathology data deposited at the National Alzheimer’s Coordinating Center (NACC) and identifiers for ADI linkage (N = 8,637; Figure 1) were included. Geocoded donor addresses were linked to time‐concordant national ADI percentiles for year of death, categorized into standard groupings of low (ADI 1‐19), medium (20‐49) and high (50‐100) ADI. Neuropathological findings were drawn from NACC and reflected standard assessment practices at time of donation. Logistic regression models, adjusted for sex and age at death, assessed relationships between high ADI and neuropathology findings. Results: Of the N = 8,637 brain donors (Table 1), 2,071 of 2,366 assessed (88%) had AD pathology by NIA‐AA criteria; 4,197 of 6,929 assessed (61%) had cerebral amyloid angiopathy; 2582 of 8092 assessed (32%) had Lewy body pathology; 391 of 2351 assessed (17%) had non‐AD tauopathy; and 586 of 1680 assessed (35%) had TDP‐43 pathology. 2,126(25%) were high ADI; 3,171(37%) medium ADI and 3,340(38%) low ADI with 51% female and average age at death of 81.9 years. As compared to low ADI donors, high ADI brain donors had adjusted odds = 1.35 (95% CI = 0.98‐1.86, p‐value = 0.06) for AD pathology; 1.10 (0.98–1.25, p = 0.11) for cerebral amyloid angiopathy; 1.37 (1.21–1.55, p<0.01) for Lewy body; 1.09 (0.83–1.44, p = 0.53) for non‐AD tauopathy; and 1.40 (1.08‐1.81, p = 0.01) for TDP‐43 pathology (Table 2). Conclusions: This first‐in‐field study provides evidence that the adverse social exposome (high ADI) is strongly associated with an increased risk of Lewy body, an increased risk of TDP‐43, and a trend towards increased AD pathology in a national cohort of brain donors.
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    Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
    (Springer Nature, 2019-03) Kunkle, Brian W.; Grenier-Boley, Benjamin; Sims, Rebecca; Bis, Joshua C.; Damotte, Vincent; Naj, Adam C.; Boland, Anne; Vronskaya, Maria; van der Lee, Sven J.; Amlie-Wolf, Alexandre; Bellenguez, Céline; Frizatti, Aura; Chouraki, Vincent; Martin, Eden R.; Sleegers, Kristel; Badarinarayan, Nandini; Jakobsdottir, Johanna; Hamilton-Nelson, Kara L.; Moreno-Grau, Sonia; Olaso, Robert; Raybould, Rachel; Chen, Yuning; Kuzma, Amanda B.; Hiltunen, Mikko; Morgan, Taniesha; Ahmad, Shahzad; Vardarajan, Badri N.; Epelbaum, Jacques; Hoffmann, Per; Boada, Merce; Beecham, Gary W.; Garnier, Jean-Guillaume; Harold, Denise; Fitzpatrick, Annette L.; Valladares, Otto; Moutet, Marie-Laure; Gerrish, Amy; Smith, Albert V.; Qu, Liming; Bacq, Delphine; Denning, Nicola; Jian, Xueqiu; Zhao, Yi; Del Zompo, Maria; Fox, Nick C.; Choi, Seung-Hoan; Mateo, Ignacio; Hughes, Joseph T.; Adams, Hieab H.; Malamon, John; Sanchez-Garcia, Florentino; Patel, Yogen; Brody, Jennifer A.; Dombroski, Beth A.; Deniz Naranjo, Maria Candida; Daniilidou, Makrina; Eiriksdottir, Gudny; Mukherjee, Shubhabrata; Wallon, David; Uphill, James; Aspelund, Thor; Cantwell, Laura B.; Garzia, Fabienne; Galimberti, Daniela; Hofer, Edith; Butkiewicz, Mariusz; Fin, Bertrand; Scarpini, Elio; Sarnowski, Chloe; Bush, Will S.; Meslage, Stéphane; Kornhuber, Johannes; White, Charles C.; Song, Yuenjoo; Barber, Robert C.; Engelborghs, Sebastiaan; Sordon, Sabrina; Voijnovic, Dina; Adams, Perrie M.; Vandenberghe, Rik; Mayhaus, Manuel; Cupples, L. Adrienne; Albert, Marilyn S.; De Deyn, Peter P.; Gu, Wei; Himali, Jayanadra J.; Beekly, Duane; Squassina, Alessio; Hartmann, Annette M.; Orellana, Adelina; Blacker, Deborah; Rodriguez-Rodriguez, Eloy; Lovestone, Simon; Garcia, Melissa E.; Doody, Rachelle S.; Munoz-Fernadez, Carmen; Sussams, Rebecca; Lin, Honghuang; Fairchild, Thomas J.; Benit, Yolanda A.; Holmes, Clive; Karamujić-Čomić, Hata; Frosch, Matthew P.; Thonberg, Hakan; Maier, Wolfgang; Roshchupkin, Gennady; Ghetti, Bernardino; Giedraitis, Vilmantas; Kawalia, Amit; Li, Shuo; Huebinger, Ryan M.; Kilander, Lena; Moebus, Susanne; Hernández, Isabel; Kamboh, M. Ilyas; Brundin, RoseMarie; Turton, James; Yang, Qiong; Katz, Mindy J.; Concari, Letizia; Lord, Jenny; Beiser, Alexa S.; Keene, C. Dirk; Helisalmi, Seppo; Kloszewska, Iwona; Kukull, Walter A.; Koivisto, Anne Maria; Lynch, Aoibhinn; Tarraga, Lluís; Larson, Eric B.; Haapasalo, Annakaisa; Lawlor, Brian; Mosley, Thomas H.; Lipton, Richard B.; Solfrizzi, Vincenzo; Gill, Michael; Longstreth, W. T., Jr.; Montine, Thomas J.; Frisardi, Vincenza; Diez-Fairen, Monica; Rivadeneira, Fernando; Petersen, Ronald C.; Deramecourt, Vincent; Alvarez, Ignacio; Salani, Francesca; Ciaramella, Antonio; Boerwinkle, Eric; Reiman, Eric M.; Fievet, Nathalie; Rotter, Jerome I.; Reisch, Joan S.; Hanon, Olivier; Cupidi, Chiara; Uitterlinden, A. G. Andre; Royall, Donald R.; Dufouil, Carole; Maletta, Raffaele Giovanni; de Rojas, Itziar; Sano, Mary; Brice, Alexis; Cecchetti, Roberta; St. George-Hyslop, Peter; Ritchie, Karen; Tsolaki, Magda; Tsuang, Debby W.; Dubois, Bruno; Craig, David; Wu, Chuang-Kuo; Soininen, Hilkka; Avramidou, Despoina; Albin, Roger L.; Fratiglioni, Laura; Germanou, Antonia; Apostolova, Liana G.; Keller, Lina; Koutroumani, Maria; Arnold, Steven E.; Panza, Francesco; Gkatzima, Olymbia; Asthana, Sanjay; Hannequin, Didier; Whitehead, Patrice; Atwood, Craig S.; Caffarra, Paolo; Hampel, Harald; Quintela, Inés; Carracedo, Ángel; Lannfelt, Lars; Rubinsztein, David C.; Barnes, Lisa L.; Pasquier, Florence; Frölich, Lutz; Barral, Sandra; McGuinness, Bernadette; Beach, Thomas G .; Johnston, Janet A.; Becker, James T.; Passmore, Peter; Bigio, Eileen H.; Schott, Jonathan M.; Bird, Thomas D.; Warren, Jason D.; Boeve, Bradley F.; Lupton, Michelle K.; Bowen, James D.; Proitsi, Petra; Boxer, Adam; Powell, John F.; Burke, James R.; Kauwe, John S.K.; Burns, Jeffrey M.; Mancuso, Michelangelo; Buxbaum, Joseph D.; Bonuccelli, Ubaldo; Cairns, Nigel J.; McQuillin, Andrew; Cao, Chuanhai; Livingston, Gill; Carlson, Chris S.; Bass, Nicholas J.; Carlsson, Cynthia M.; Hardy, John; Carney, Regina M.; Bras, Jose; Carrasquillo, Minerva M.; Guerreiro, Rita; Allen, Mariet; Chui, Helena C.; Fisher, Elizabeth; Masullo, Carlo; Crocco, Elizabeth A.; DeCarli, Charles; Bisceglio, Gina; Dick, Malcolm; Ma, Li; Duara, Ranjan; Graff-Radford, Neill R.; Evans, Denis A.; Hodges, Angela; Faber, Kelley M.; Scherer, Martin; Fallon, Kenneth B.; Riemenschneider, Matthias; Fardo, David W.; Heun, Reinhard; Farlow, Martin R.; Kölsch, Heike; Ferris, Steven; Leber, Markus; Foroud, Tatiana M.; Heuser, Isabella; Galasko, Douglas R.; Giegling, Ina; Gearing, Marla; Hüll, Michael; Geschwind, Daniel H.; Gilbert, John R.; Morris, John; Green, Robert C.; Mayo, Kevin; Growdon, John H.; Feulner, Thomas; Hamilton, Ronald L.; Harrell, Lindy E.; Drichel, Dmitriy; Honig, Lawrence S.; Cushion, Thomas D.; Huentelman, Matthew J.; Hollingworth, Paul; Hulette, Christine M.; Hyman, Bradley T.; Marshall, Rachel; Jarvik, Gail P.; Meggy, Alun; Abner, Erin; Menzies, Georgina E.; Jin, Lee-Way; Leonenko, Ganna; Real, Luis M.; Jun, Gyungah R.; Baldwin, Clinton T.; Grozeva, Detelina; Karydas, Anna; Russo, Giancarlo; Kaye, Jeffrey A.; Kim, Ronald; Jessen, Frank; Kowall, Neil W.; Vellas, Bruno; Kramer, Joel H.; Vardy, Emma; LaFerla, Frank M.; Jöckel, Karl-Heinz; Lah, James J.; Dichgans, Martin; Leverenz, James B.; Mann, David; Levey, Allan I.; Pickering-Brown, Stuart; Lieberman, Andrew P.; Klopp, Norman; Lunetta, Kathryn L.; Wichmann, H-Erich; Lyketsos, Constantine G.; Morgan, Kevin; Marson, Daniel C.; Brown, Kristelle; Martiniuk, Frank; Medway, Christopher; Mash, Deborah C.; Nöthen, Markus M.; Masliah, Eliezer; Hooper, Nigel M.; McCormick, Wayne C.; Daniele, Antonio; McCurry, Susan M.; Bayer, Anthony; McDavid, Andrew N.; Gallacher, John; McKee, Ann C.; van den Bussche, Hendrik; Mesulam, Marsel; Brayne, Carol; Miller, Bruce L.; Riedel-Heller, Steffi; Miller, Carol A.; Miller, Joshua W.; Al-Chalabi, Ammar; Morris, John C.; Shaw, Christopher E.; Myers, Amanda J.; Wiltfang, Jens; O'Bryant, Sid; Olichney, John M.; Alvarez, Victoria; Parisi, Joseph E.; Singleton, Andrew B.; Paulson, Henry L.; Collinge, John; Perry, William R.; Mead, Simon; Peskind, Elaine; Cribbs, David H.; Rossor, Martin; Pierce, Aimee; Ryan, Natalie S.; Poon, Wayne W.; Nacmias, Benedetta; Potter, Huntington; Sorbi, Sandro; Quinn, Joseph F.; Sacchinelli, Eleonora; Raj, Ashok; Spalletta, Gianfranco; Raskind, Murray; Caltagirone, Carlo; Bossù, Paola; Orfei, Maria Donata; Reisberg, Barry; Clarke, Robert; Reitz, Christiane; Smith, A. David; Ringman, John M.; Warden, Donald; Roberson, Erik D.; Wilcock, Gordon; Rogaeva, Ekaterina; Bruni, Amalia Cecilia; Rosen, Howard J.; Gallo, Maura; Rosenberg, R.N.; Ben-Shlomo, Yoav; Sager, Mark A.; Mecocci, Patrizia; Saykin, Andrew J.; Pastor, Pau; Cuccaro, Michael L.; Vance, Jeffery M.; Schneider, Julie A.; Schneider, Lori S.; Slifer, Susan; Seeley, William W.; Smith, Amanda G.; Sonnen, Joshua A.; Spina, Salvatore; Stern, Robert A.; Swerdlow, Russell H.; Tang, Mitchell; Tanzi, Rudolph E.; Trojanowski, John Q.; Troncoso, Juan C.; Van Deerlin, Vivianna M.; Van Eldik, Linda J.; Vinters, Harry V.; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A.; Wilhelmsen, Kirk C.; Williamson, Jennifer; Wingo, Thomas S.; Woltjer, Randall L.; Wright, Clinton B.; Yu, Chang-En; Yu, Lei; Saba, Yasaman; Pilotto, Alberto; Bullido, Maria J.; Peters, Oliver; Crane, Paul K.; Bennett, David; Bosco, Paola; Coto, Eliecer; Boccardi, Virginia; De Jager, Phil L.; Lleo, Alberto; Warner, Nick; Lopez, Oscar L.; Ingelsson, Martin; Deloukas, Panagiotis; Cruchaga, Carlos; Graff, Caroline; Gwilliam, Rhian; Fornage, Myriam; Goate, Alison M.; Sanchez-Juan, Pascual; Kehoe, Patrick G.; Amin, Najaf; Ertekin-Taner, Nilifur; Berr, Claudine; Debette, Stéphanie; Love, Seth; Launer, Lenore J.; Younkin, Steven G.; Dartigues, Jean-Francois; Corcoran, Chris; Ikram, M. Arfan; Dickson, Dennis W.; Nicolas, Gael; Campion, Dominique; Tschanz, JoAnn; Schmidt, Helena; Hakonarson, Hakon; Clarimon, Jordi; Munger, Ron; Schmidt, Reinhold; Farrer, Lindsay A.; Van Broeckhoven, Christine; O'Donovan, Michael C.; DeStefano, Anita L.; Jones, Lesley; Haines, Jonathan L.; Deleuze, Jean-Francois; Owen, Michael J.; Gudnason, Vilmundur; Mayeux, Richard; Escott-Price, Valentina; Psaty, Bruce M.; Ramirez, Alfredo; Wang, Li-San; Ruiz, Agustin; van Duijn, Cornelia M.; Holmans, Peter A.; Seshadri, Sudha; Williams, Julie; Amouyel, Phillippe; Schellenberg, Gerard D.; Lambert, Jean-Charles; Pericak-Vance, Margaret A.; Pathology and Laboratory Medicine, School of Medicine
    Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
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    Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel
    (American Medical Association, 2021-01-01) Kunkle, Brian W.; Schmidt, Michael; Klein, Hans-Ulrich; Naj, Adam C.; Hamilton-Nelson, Kara L.; Larson, Eric B.; Evans, Denis A.; De Jager, Phil L.; Crane, Paul K.; Buxbaum, Joe D.; Ertekin-Taner, Nilufer; Go, Rodney C.P.; Obisesan, Thomas O.; Kamboh, Ilyas; Bennett, David A.; Hall, Kathleen S.; Goate, Alison M.; Foroud, Tatiana M.; Martin, Eden R.; Wang, Li-Sao; Byrd, Goldie S.; Farrer, Lindsay A.; Haines, Jonathan L.; Schellenberg, Gerard D.; Mayeux, Richard; Pericak-Vance, Margaret A.; Reitz, Christiane; Graff-Radford, Neill R.; Martinez, Izri; Ayodele, Temitope; Logue, Mark W.; Cantwell, Laura B.; Jean-Francois, Melissa; Kuzma, Amanda B.; Adams, L.D.; Vance, Jeffery M.; Cuccaro, Michael L.; Chung, Jaeyoon; Mez, Jesse; Lunetta, Kathryn L.; Jun, Gyungah R.; Lopez, Oscar L.; Hendrie, Hugh C.; Reiman, Eric M.; Kowall, Neil W.; Leverenz, James B.; Small, Scott A.; Levey, Allan I.; Golde, Todd E.; Saykin, Andrew J.; Starks, Takiyah D.; Albert, Marilyn S.; Hyman, Bradley T.; Petersen, Ronald C.; Sano, Mary; Wisniewski, Thomas; Vassar, Robert; Kaye, Jeffrey A.; Henderson, Victor W.; DeCarli, Charles; LaFerla, Frank M.; Brewer, James B.; Miller, Bruce L.; Swerdlow, Russell H.; Van Eldik, Linda J.; Paulson, Henry L.; Trojanowski, John Q.; Chui, Helena C.; Rosenberg, Roger N.; Craft, Suzanne; Grabowski, Thomas J.; Asthana, Sanjay; Morris, John C.; Strittmatter, Stephen M.; Kukull, Walter A.; Psychiatry, School of Medicine
    Importance: Compared with non-Hispanic White individuals, African American individuals from the same community are approximately twice as likely to develop Alzheimer disease. Despite this disparity, the largest Alzheimer disease genome-wide association studies to date have been conducted in non-Hispanic White individuals. In the largest association analyses of Alzheimer disease in African American individuals, ABCA7, TREM2, and an intergenic locus at 5q35 were previously implicated. Objective: To identify additional risk loci in African American individuals by increasing the sample size and using the African Genome Resource panel. Design, setting, and participants: This genome-wide association meta-analysis used case-control and family-based data sets from the Alzheimer Disease Genetics Consortium. There were multiple recruitment sites throughout the United States that included individuals with Alzheimer disease and controls of African American ancestry. Analysis began October 2018 and ended September 2019. Main outcomes and measures: Diagnosis of Alzheimer disease. Results: A total of 2784 individuals with Alzheimer disease (1944 female [69.8%]) and 5222 controls (3743 female [71.7%]) were analyzed (mean [SD] age at last evaluation, 74.2 [13.6] years). Associations with 4 novel common loci centered near the intracellular glycoprotein trafficking gene EDEM1 (3p26; P = 8.9 × 10-7), near the immune response gene ALCAM (3q13; P = 9.3 × 10-7), within GPC6 (13q31; P = 4.1 × 10-7), a gene critical for recruitment of glutamatergic receptors to the neuronal membrane, and within VRK3 (19q13.33; P = 3.5 × 10-7), a gene involved in glutamate neurotoxicity, were identified. In addition, several loci associated with rare variants, including a genome-wide significant intergenic locus near IGF1R at 15q26 (P = 1.7 × 10-9) and 6 additional loci with suggestive significance (P ≤ 5 × 10-7) such as API5 at 11p12 (P = 8.8 × 10-8) and RBFOX1 at 16p13 (P = 5.4 × 10-7) were identified. Gene expression data from brain tissue demonstrate association of ALCAM, ARAP1, GPC6, and RBFOX1 with brain β-amyloid load. Of 25 known loci associated with Alzheimer disease in non-Hispanic White individuals, only APOE, ABCA7, TREM2, BIN1, CD2AP, FERMT2, and WWOX were implicated at a nominal significance level or stronger in African American individuals. Pathway analyses strongly support the notion that immunity, lipid processing, and intracellular trafficking pathways underlying Alzheimer disease in African American individuals overlap with those observed in non-Hispanic White individuals. A new pathway emerging from these analyses is the kidney system, suggesting a novel mechanism for Alzheimer disease that needs further exploration. Conclusions and relevance: While the major pathways involved in Alzheimer disease etiology in African American individuals are similar to those in non-Hispanic White individuals, the disease-associated loci within these pathways differ.
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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.