Impact of regional amyloid and tau on diffusion FA at the gray/white interface in sporadic AD
Poster No:
103
Submission Type:
Abstract Submission
Authors:
David Hoagey1, Nicole McKay1, Qing Wang1, Brian Gordon1, Tammie Benzinger1
Institutions:
1Washington University in St. Louis, St. Louis, MO
First Author:
Co-Author(s):
Introduction:
Clinical pathology and staging of Alzheimer disease (AD) is characterized by the temporal progression of amyloid accumulation, tau deposition, and eventually cortical neurodegeneration. Despite this temporal ordering, research is mixed regarding the regional impact of amyloid and tau on neurodegeneration and subsequent cognitive declines. With the advent of anti-amyloid therapies, it is critical to understand these relationships and the biological underpinning of neurodegeneration to better assess the impact of protein clearance on neuronal health and cognition. Diffusion magnetic resonance imaging (MRI) has proven to be sensitive to changes in tissue microstructure with fractional anisotropy (FA) serving as a proxy of cytoarchitectural boundaries, an indicator of fiber complexity and neuronal health. Diffusion-based imaging in gray and white matter has shown the capability to detect early presymptomatic changes, track conversion across symptomatic stages, and distinguish between AD subtypes. Additionally, assessing neuronal health from tissue signal metrics at the gray/white interface has shown to be sensitive to neurodegeneration that precedes cortical atrophy. Here we analyze the impact of regional amyloid and tau on diffusion metrics within the gray/white interface to assess microstructural aspects of neuronal health.
Methods:
Participants were recruited by the Knight Alzheimer Disease Research Center at the Washington University School of Medicine. To date, data from a total of 354 participants have been acquired and processed across all imaging sequences, including T1-weighted and diffusion MRI and amyloid and tau positron emission tomography (PET). Participants had an average age of 68.13 years, with 57.9% (205) being female, 87.6% (310) identifying as white, and 15.8% (56) having a Clinical Dementia Rating greater than 0. T1-weighted data was processed using FreeSurfer to generate regions of interest from the Desikan-Killiany atlas. Each region was dilated by 3 voxels into the gray/white interface and registered into participant diffusion space to extract FA. PET imaging data was processed using the PET Unified Pipeline to generate Standardized Uptake Value Ratio (SUVR) values in the same atlas. General linear models assessed the regional effects of amyloid and tau SUVR with the corresponding FA values.
Results:
Results show regionally differential effects on FA for each of amyloid and tau burden. Increases in amyloid have a broad impact on diffusion across many of the higher-order association cortices, with a pattern comparable to that of typical amyloid deposition. Specifically, we observed increased FA in the frontal, parietal, and superior temporal cortices with higher amyloid burden. In contrast, tau accumulation had a much more focused impact. Increased tau was related to decreasing FA in medial temporal, occipital, and lateral frontal areas, similar to typical patterns of tau spread. Limbic areas demonstrate consistent increases in FA with increasing amyloid and tau, implying unique vulnerability of neuronal health in regions critical to memory performance.
Conclusions:
Microstructural features of neuronal health, as proxied from diffusion imaging, are highly associated with the spread of protein biomarkers in AD. Regional patterns appear to mimic the spread of amyloid and tau in presymptomatic stages of sporadic AD and could reflect initial neurodegenerative processes such as changes in fiber complexity or increasing inflammatory processes. Assessing the health of the gray/white interface might provide an early indicator of changes to myelin integrity or cytoarchitectural fiber complexity cause by increased cytotoxicity or microglial activation. These findings help to disentangle the neurodegenerative aspects of AD by improving the biological specificity of neurodegeneration as a biomarker, characterizing the regional and temporal relationships with amyloid and tau, and illuminating the mechanisms driving the earliest cognitive declines.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Cortical Cyto- and Myeloarchitecture
Novel Imaging Acquisition Methods:
Diffusion MRI 2
PET
Keywords:
Cognition
Data analysis
Degenerative Disease
MRI
Neuron
Positron Emission Tomography (PET)
STRUCTURAL MRI
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Alzheimer disease
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Are you Internal Review Board (IRB) certified? Please note: Failure to have IRB, if applicable will lead to automatic rejection of abstract.
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
For human MRI, what field strength scanner do you use?
Which processing packages did you use for your study?
Provide references using APA citation style.
Aung, W. Y., et al. (2013). Diffusion tensor MRI as a biomarker in axonal and myelin damage. Imaging in medicine, 5(5), 427.
Jack Jr, C. R., et al. (2018). NIA‐AA research framework: toward a biological definition of Alzheimer's disease. Alzheimer's & Dementia, 14(4), 535-562.
Jefferson, A. L., et al. (2015). Gray & white matter tissue contrast differentiates Mild Cognitive Impairment converters from non-converters. Brain imaging and behavior, 9, 141-148.
Kroenke, C. D. (2018). Using diffusion anisotropy to study cerebral cortical gray matter development. Journal of Magnetic Resonance, 292, 106-116.
Torso, M., et al. (2023). In vivo cortical diffusion imaging relates to Alzheimer’s disease neuropathology. Alzheimer's Research & Therapy, 15(1), 165.
Weston, P. S., et al. (2015). Diffusion imaging changes in grey matter in Alzheimer’s disease: a potential marker of early neurodegeneration. Alzheimer's Research & Therapy, 7, 1-8.