Poster K4 - The association between tau PET and white matter integrity in aging and Alzheimer's Disease

Friday, October 25, 2024

3:30 PM - 4:30 PM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

ZC

Zacheus Carr

Undergraduate Researcher
Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
Mahomet, Illinois, United States

Co-Author(s)

AS

Aditi Sathe, MS

Senior Statistical Genetic Analyst
Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA, United States
DZ

Dimitrios Zaras

Data Scientist Assistant 1
Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA, United States
Alaina Durant, BS (she/her/hers)

Statistical Genetic Analyst
Vanderbilt Memory and Alzheimer's Center
Westmoreland, Tennessee, United States
MK

Michael Kim

Graduate Student
Department of Computer Science- Vanderbilt, United States
Chenyu Gao, MS (he/him/his)

Graduate Student
Department of Electrical and Computer Engineering- Vanderbilt University
Nashville, Tennessee, United States
Nazirah Mohd Khairi, PhD (she/her/hers)

Postdoctoral Researcher
Department of Electrical and Computer Engineering- Vanderbilt University, United States
Zhiyuan Li, PhD (he/him/his)

Postdoctoral Researcher
Department of Electrical and Computer Engineering- Vanderbilt University, United States
TY

Tianyuan Yao

Graduate Student
Department of Computer Science- Vanderbilt, United States
YH

Yuankai Huo

Assistant Professor
Department of Computer Science, and Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, 37235, USA, United States
LD

Logan Dumitrescu

Assistant Professor, Neurology
Vanderbilt Memory and Alzheimer's Center, United States
PZ

Panpan Zhang

Assistant Professor
Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Department of Biostatistics, Vanderbilt University Medical Center, United States
Bennett Landman, PhD

Professor
Vanderbilt University, United States
AJ

Angela Jefferson

Professor
Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Department of Neurology, Vanderbilt University Medical Center, Department of Computer Science, Vanderbilt University, United States
TH

Timothy Hohman

Professor
Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Department of Neurology, Vanderbilt Genetics Institute, Vanderbilt Brain Institute, Vanderbilt University Medical Center, United States

Last Author(s)

Derek Archer, PhD

Assistant Professor, Neurology
Vanderbilt Memory and Alzheimer's Center, United States

Introduction: Alzheimer's Disease (AD) is the most common form of dementia affecting nearly seven million Americans. Currently, there are no cures and only a few mildly effective treatments for AD. Pathologically, AD is characterized by the presence of both tau proteins and amyloid plaques. Tau proteins are intracellular proteins that stabilize microtubules in neurons. In AD, these proteins become hyperphosphorylated, leading to the formation of neurofibrillary tangles (NFTs). Previous research has shown that NFTs disrupt the cell's transport system, contributing to neuronal death and cognitive impairment. Amyloid plaques are extracellular deposits of amyloid-beta peptides that accumulate in the brain, disrupting cell-to-cell communication and triggering inflammatory responses. These plaques contribute to the neurodegeneration and cognitive decline observed in AD.
Studying the effects of tau proteins and amyloid plaques on white matter integrity in the brain could provide better insight into the early symptoms of AD, potentially leading to more viable treatments.

Materials and

Methods: This is a cross-sectional study that investigates how tau proteins and amyloid plaques affect white matter integrity (WMI) using data from a cohort of elderly patients (n=487 for amyloid and n=338 for tau). The cohort variables of interest include PET scan SUVR data providing both continuous and binary measures of tau proteins and amyloid plaques. Diffusion MRI data was used to assess 48 white matter tracts (WMT) in the brain, quantifying both free water (FW) and FW-corrected fractional anisotropy (FAfwcorr) as measures of WMI. The primary analysis consisted of a linear regression analysis that measured the effects of tau on WMI. The variable used to measure tau was continuous, and measured tau in early Braak Stages (1 and 2). WMI was assessed using the 48 WMT by using both FW and FAfwcorr measures. Additionally, the regression was adjusted for age, sex, education, amyloid positivity, and radiotracer type. The significance level was 0.05 and the FDR corrections were considered for multiple testing. The subgroup analyses stratified the data based on amyloid presence. After splitting the data, the total sample size included 230 participants (126 amyloid negative, 104 amyloid positive). The linear regression analyses for amyloid positive and negative were conducted in the same manner as in the primary analysis except for the amyloid positivity covariate.

Results, Conclusions, and Discussions: In the primary analysis, 11 unique tracts were deemed significant. The most significant finding was with FW in the cingulum bundle, which is a critical part of the limbic system and plays a key role in the memory and emotional functions of the brain. Other significant brain regions included the frontal, temporal, parietal, and occipital lobes, indicating widespread significance across the brain. All associations between FAfwcorr and tau were negative, whereas all associations between FW and tau were positive. This pattern aligns with the expected opposite correlations between FAfwcorr and FW and indicates that increasing tau levels lead to decreased WMI. The subgroup analysis showed 17 unique significant tracts, with every significant result occurring in the amyloid-positive group. The limbic, frontal, and temporal lobes were once again key areas of significance, with the cingulum bundle being the most significant tract (Figure 1). These findings provide critical insights into the brain regions most affected by tau pathology in AD. The involvement of the frontal, temporal, parietal, and occipital lobes underscores the widespread effect of tau pathology on various cognitive and sensory functions, while the cingulum bundle once again highlights the memory and emotional decline that is commonly associated with AD. The observation that significant results were only found in the amyloid-present group during the stratified subgroup analysis shows a likely correlation between tau proteins and amyloid plaques that is further investigated later . This interaction may strengthen the degeneration of WMI, suggesting that amyloid presence amplifies the detrimental effects of tau on the brain. These results highlight the necessity of considering both pathological markers in AD research and treatment strategies opening doors for future research regarding the interactions between the two. Understanding the areas affected by tau proteins and amyloid plaques during the early stages of the disease can help localize treatments to targeted areas. A better understanding of the relationship and interactions between tau and amyloid can guide treatment options to prevent the spread of both, maintaining higher WMI and brain function in individuals with AD.

Acknowledgements (Optional):