Sherry A Ferguson1, John J Panos1, Daniel Sloper2, Vijayalakshmi Varma2. 1. Division of Neurotoxicology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR, USA. 2. Division of Systems Biology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR, USA.
Abstract
BACKGROUND: Alzheimer's disease (AD) presents with an earlier onset age and increased symptom severity in African Americans and Hispanics. OBJECTIVE: Although the prevalence of plaques and tangles may not exhibit ethnicity-related differences, levels of neurodegenerative proteins have not been described. METHODS: Here, levels of five proteins (i.e., S100B, sRAGE, GDNF, Aβ40, and Aβ42) and the Aβ42/Aβ40 ratio were measured in postmortem samples of the middle temporal gyrus (BA21) from age-matched African Americans and Caucasians with AD (n = 6/gender/ethnicity). RESULTS: S100B levels were increased 17% in African Americans (p < 0.003) while sRAGE was mildly decreased (p < 0.09). Aβ42 levels were increased 121% in African Americans (p < 0.02), leading to a 493% increase in the Aβ42/Aβ40 ratio (p < 0.002). Analysis of GDNF levels did not indicate any significant effects. There were no significant effects of gender and no significant ethnicity with gender interactions on any analyte. Effect size calculations indicated "medium" to "very large" effects. CONCLUSION: S100B is typically elevated in AD cases; however, the increased levels in African Americans here may be indicative of increased severity in specific populations. Increased Aβ42/Aβ40 ratios in the current study are compatible with increased disease severity and might indicate increased AD pathogenesis in African Americans. Overall, these results are compatible with a hypothesis of increased neuroinflammation in African Americans with AD.
BACKGROUND:Alzheimer's disease (AD) presents with an earlier onset age and increased symptom severity in African Americans and Hispanics. OBJECTIVE: Although the prevalence of plaques and tangles may not exhibit ethnicity-related differences, levels of neurodegenerative proteins have not been described. METHODS: Here, levels of five proteins (i.e., S100B, sRAGE, GDNF, Aβ40, and Aβ42) and the Aβ42/Aβ40 ratio were measured in postmortem samples of the middle temporal gyrus (BA21) from age-matched African Americans and Caucasians with AD (n = 6/gender/ethnicity). RESULTS:S100B levels were increased 17% in African Americans (p < 0.003) while sRAGE was mildly decreased (p < 0.09). Aβ42 levels were increased 121% in African Americans (p < 0.02), leading to a 493% increase in the Aβ42/Aβ40 ratio (p < 0.002). Analysis of GDNF levels did not indicate any significant effects. There were no significant effects of gender and no significant ethnicity with gender interactions on any analyte. Effect size calculations indicated "medium" to "very large" effects. CONCLUSION:S100B is typically elevated in AD cases; however, the increased levels in African Americans here may be indicative of increased severity in specific populations. Increased Aβ42/Aβ40 ratios in the current study are compatible with increased disease severity and might indicate increased AD pathogenesis in African Americans. Overall, these results are compatible with a hypothesis of increased neuroinflammation in African Americans with AD.
Authors: Mariko Sawa; Cassia Overk; Ann Becker; Dominique Derse; Ricardo Albay; Kim Weldy; Ahmad Salehi; Thomas G Beach; Eric Doran; Elizabeth Head; Y Eugene Yu; William C Mobley Journal: Alzheimers Dement Date: 2021-11-10 Impact factor: 16.655