Elevated ARTS Scores Correlate with Increased NfL Levels but Not p-Tau217.
Poster No:
156
Submission Type:
Abstract Submission
Authors:
Gulam Mahfuz Chowdhury1, Khalid Saifullah1, Arnold Evia2, David Bennett2, Julie Schneider2, Konstantinos Arfanakis1
Institutions:
1Illinois Institute of Technology, Chicago, IL, 2Rush University Medical Center, Chicago, IL
First Author:
Co-Author(s):
Introduction:
Intracranial arteriolosclerosis, one of the main pathologies of cerebral small vessel disease (CSVD), has a significant impact on cerebrovascular health and cognition(Wardlaw et al., 2013), and is more severe in female(Oveisgharan et al., 2018). ARTS(Makkinejad et al., 2021) is an MRI-based marker of arteriolosclerosis, and is the first to provide in-vivo insight about the presence of arteriolosclerosis pathology. Since ARTS was introduced very recently, it is not yet known how it relates to markers of other brain pathologies, especially Alzheimer's, and neuronal damage. Phosphorylated tau 217 (p-tau217) is a blood-based biomarker for Alzheimer's disease pathology(Ashton et al., 2024), and plasma neurofilament light chain (NfL) is a biomarker of both neurodegenerative-related and vascular-related axonal damage(Khalil et al., 2018). In this work, we investigated the association of ARTS with blood-based biomarkers p-tau217 and NfL.
Methods:
Participants and data collection:
This study included 202 participants from four longitudinal, clinical-pathologic cohort studies of aging: the Rush Memory and Aging Project (MAP), Religious Orders Study, Minority Aging Research Study, and the African American Clinical Core of the Rush Alzheimer's Disease Research Center. This sample included only participants with no or mild cognitive impairment. None of the participants had dementia.
All participants underwent in-vivo MRI on 3 Tesla MRI scanners using MPRAGE, FLAIR, and DTI sequences. The MRI data were used to calculate ARTS scores for all participants using the fully-automated, publicly available ARTS software. Blood was collected on all participants. plasma p-tau217 and NfL levels were measured at the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) using established procedures(Edwards et al., 2024). Quality was ensured by using control samples and pooled plasma references to maintain consistency. Both p-tau217 and NfL values were log transformed to normalize the distribution.
Statistical Analyses:
Linear regression was used to test the association of ARTS score with levels of p-tau217 and NfL, separately, controlling for demographics (age at visit, sex, years of education), interval between blood draw and MRI scanning, and scanner (Fig. 1). The FSL PALM tool with 10000 permutations and tail acceleration was used for the statistical analysis(Winkler et al., 2014). Associations were considered significant at p<0.05 after family-wise error (FWE) correction.
This study included 202 participants from four longitudinal, clinical-pathologic cohort studies of aging: the Rush Memory and Aging Project (MAP), Religious Orders Study, Minority Aging Research Study, and the African American Clinical Core of the Rush Alzheimer's Disease Research Center. This sample included only participants with no or mild cognitive impairment. None of the participants had dementia.
All participants underwent in-vivo MRI on 3 Tesla MRI scanners using MPRAGE, FLAIR, and DTI sequences. The MRI data were used to calculate ARTS scores for all participants using the fully-automated, publicly available ARTS software. Blood was collected on all participants. plasma p-tau217 and NfL levels were measured at the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) using established procedures(Edwards et al., 2024). Quality was ensured by using control samples and pooled plasma references to maintain consistency. Both p-tau217 and NfL values were log transformed to normalize the distribution.
Statistical Analyses:
Linear regression was used to test the association of ARTS score with levels of p-tau217 and NfL, separately, controlling for demographics (age at visit, sex, years of education), interval between blood draw and MRI scanning, and scanner (Fig. 1). The FSL PALM tool with 10000 permutations and tail acceleration was used for the statistical analysis(Winkler et al., 2014). Associations were considered significant at p<0.05 after family-wise error (FWE) correction.
·Fig. 1
Results:
No significant association of ARTS scores with levels of p-tau217 was detected (β=0.0046, p=0.38), underscoring that ARTS is independent of Alzheimer's pathology(Fig.2A). In contrast, a strong positive association of ARTS with NfL was observed (β=0.0485, p=0.0011), highlighting that ARTS is linked to CSVD-related axonal injury(Fig.2B).
·Fig. 2
Conclusions:
The present study in 202 community-based older adults without dementia showed that the ARTS in-vivo marker of arteriolosclerosis is not related with blood-based marker p-tau217, but is positively associated with NfL. The fact that ARTS score is independent of the level of p-tau217 suggests that ARTS, which is an MRI-based marker, is not influenced by brain changes associated with Alzheimer's and p-tau217. This is of high significance because arteriolosclerosis often co-occurs with AD pathology in the community, and a successful marker of arteriolosclerosis must be independent of Alzheimer's to be able to identify arteriolosclerosis even in the presence of AD. The present study demonstrates that ARTS achieves the goal of being independent of p-tau217 levels and AD. In addition, the observed positive association between ARTS and neurofilament light (NfL), an established marker of axonal injury, supports the relevance of ARTS as a marker of vascular-related tissue injury. This relationship implies that more severe arteriolosclerosis pathology is associated with more severe axonal damage as evidenced by higher NfL levels.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Lifespan Development:
Aging 2
Keywords:
Aging
Blood
MRI
1|2Indicates the priority used for review
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