Browsing by Author "Willette, Auriel A."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Analysis and interpretation of inflammatory fluid markers in Alzheimer's disease: a roadmap for standardization
    (Springer Nature, 2025-04-15) Bettcher, Brianne M.; de Oliveira, Fabricio Ferreira; Willette, Auriel A.; Michalowska, Malgorzata M.; Santos Machado, Luiza; Rajbanshi, Binita; Borelli, Wyllians V.; Gámez Tansey, Malú; Rocha, Andréia; Suryadevara, Vidyani; Hu, William T.; Neurology, School of Medicine
    Growing interest in the role of the immune response in Alzheimer's Disease and related dementias (ADRD) has led to widespread use of fluid inflammatory markers in research studies. To standardize the use and interpretation of inflammatory markers in AD research, we build upon prior guidelines to develop consensus statements and recommendations to advance application and interpretation of these markers. In this roadmap paper, we propose a glossary of terms related to the immune response in the context of biomarker discovery/validation, discuss current conceptualizations of inflammatory markers in research, and recommend best practices to address key knowledge gaps. We also provide consensus principles to summarize primary conceptual, methodological, and interpretative issues facing the field: (1) a single inflammatory marker is likely insufficient to describe an entire biological cascade, and multiple markers with similar or distinct functions should be simultaneously measured in a panel; (2) association studies in humans are insufficient to infer causal relationships or mechanisms; (3) neuroinflammation displays time-dependent and disease context-dependent patterns; (4) neuroinflammatory mechanisms should not be inferred based solely on blood inflammatory marker changes; and (5) standardized reporting of CSF inflammatory marker assay validation and performance will improve incorporation of inflammatory markers into the biological AD criteria.
  • Thumbnail Image
    Item
    APOE, TOMM40, and Sex Interactions on Neural Network Connectivity
    (Elsevier, 2022) Li, Tianqi; Pappas, Colleen; Le, Scott T.; Wang, Qian; Klinedinst, Brandon S.; Larsen, Brittany; Pollpeter, Amy; Lee, Ling Yi; Lutz, Mike W.; Gottschalk, William K.; Swerdlow, Russell H.; Nho, Kwangsik; Willette, Auriel A.; Radiology and Imaging Sciences, School of Medicine
    The Apolipoprotein E ε4 (APOE ε4) haplotype is the strongest genetic risk factor for late-onset Alzheimer‟s disease (AD). The Translocase of Outer Mitochondrial Membrane-40 (TOMM40) gene maintains cellular bioenergetics, which is disrupted in AD. TOMM40 rs2075650 (‘650) G vs. A carriage is consistently related to neural and cognitive outcomes, but it is unclear if and how it interacts with APOE. We examined 21 orthogonal neural networks among 8,222 middle-aged to aged participants in the UK Biobank cohort. ANOVA and multiple linear regression tested main effects and interactions with APOE and TOMM40 ‘650 genotypes, and if age and sex acted as moderators. APOE ε4 was associated with less strength in multiple networks, while ‘650 G vs. A carriage was related to more language comprehension network strength. In APOE ε4 carriers, ‘650 G-carriage led to less network strength with increasing age, while in non G-carriers this was only seen in women but not men. TOMM40 may shift what happens to network activity in aging APOE ε4 carriers depending on sex.