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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
Published on: January 28, 2014
Biomarkers
Jianqiao Tian1,2, Wen Zhang3, Sheelakumari Raghavan1
1Mayo Clinic, Rochester, MN, USA.
Background:
White matter (WM) plays a dual role in interacting with tau pathology. There is an intricate dynamic relationship with WM acting as highways for tau spreading, while the increasing tau burden ultimately compromises WM health. We aimed at studying the associations between tau accumulation and WM integrity using longitudinal data with focus on sex differences.
Method:
We included 374 participants who had longitudinal multishell diffusion MRI and flortaucipir PET (baseline mean age = 70.9 years, 52% male, 17% MCI/AD dementia) scans from the Mayo ADRC and Mayo Clinic Study of Aging. Rate of tau accumulation was calculated from the entorhinal cortex (ERC) and inferior temporal cortex (IT) SUVRs, with IT-WM serving as the WM highway between the two regions. IT-WM was defined by JHU "Eve" WM atlas, and its integrity was assessed using neurite density index (NDI), which reflects the packing density of neurites. Structural equation modeling (SEM) evaluated relationships between tau and WM metrics.
Result:
At baseline, males and females showed no significant differences in tau SUVR or IT-WM NDI (p >0.05), though males had higher vascular risk and averaged two years older than females (Table 1). Figure 1a showed that baseline ERC-tau influenced baseline IT-tau, as well as both rate of ERC-tau and baseline IT-tau influenced rate of IT-tau. After incorporating IT-WM NDI as a mediator (Figure 1b), we discovered 1) baseline ERC-tau influencing rate of IT-tau accumulation through baseline IT-WM NDI, suggesting the role of WM health in the rate of tau accumulation; 2) Rate of IT-tau accumulation negatively affected follow-up IT-WM NDI suggesting the deterioration of WM health as tau accumulation progresses. These relationships were stronger in males compared to females. We also observed greater impact of vascular risk on WM health in males and greater rates of IT-tau accumulation in females.
Conclusion:
Our work sheds light on the mechanistic role of intact WM in tau accumulation (through dense microtubules and synaptic connections) and the deterioration of WM that is associated with higher rates of tau accumulation. We found interesting sex differences that warrant further investigation.
Insights
White matter integrity influences tau accumulation rates, with tau progression further damaging white matter. These associations, particularly the impact of vascular risk and tau accumulation on white matter, show notable sex differences.
Area of Science:
- Neuroimaging
- Neurodegenerative Diseases
- White Matter Integrity
Background:
- White matter (WM) facilitates tau pathology spread but is also compromised by tau accumulation.
- Understanding the dynamic relationship between tau and WM is crucial for neurodegenerative disease research.
Purpose of the Study:
- To investigate the longitudinal associations between tau accumulation and white matter (WM) integrity.
- To explore potential sex differences in these relationships.
Main Methods:
- Utilized longitudinal diffusion MRI and flortaucipir PET data from 374 participants.
- Assessed WM integrity using neurite density index (NDI) in the inferior temporal-white matter (IT-WM) tract.
- Employed structural equation modeling (SEM) to analyze relationships between tau metrics and WM integrity.
Main Results:
- Baseline tau levels influenced the rate of subsequent tau accumulation, mediated by IT-WM integrity.
- Progressive tau accumulation was associated with a decline in IT-WM neurite density index (NDI).
- These relationships were more pronounced in males, who also showed greater vascular risk impact on WM health and higher rates of tau accumulation in females.
Conclusions:
- Intact white matter plays a mechanistic role in modulating tau accumulation.
- Deterioration of white matter is linked to increased rates of tau accumulation.
- Significant sex differences in the tau-WM relationship warrant further investigation.
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