INS NYC 2024 Program

Poster	Poster Session 03 Program Schedule 02/15/2024 09:30 am - 10:40 am Room: Shubert Complex (Posters 1-60) Poster Session 03: Neurotrauma \| Neurovascular Final Abstract #20 Vascular disease drives Alzheimer’s disease biomarker concentrations in adults with Down syndrome Natalie Edwards, Columbia University, New York, United States Patrick Lao, Columbia University, New York, United States Olivia Ericsson, Columbia University, New York, United States Mohamad Alshikho, Columbia University, New York, United States Batool Rizvi, University of California, Irvine, Irvine, United States Lisi Flores Aguilar, University of California, Irvine, Irvine, United States Melissa Petersen, University of North Texas, Fort Worth, United States Sid O'Bryant, University of North Texas, Fort Worth, United States Dana Tudorascu, University of Pittsburgh, Pittsburgh, United States José Gutierrez, Columbia University, New York, United States Donna Wilcock, Indiana University, Indianapolis, United States Elizabeth Head, University of California, Irvine, Irvine, United States Adam Brickman, Columbia University, New York, United States Category: Neuroimaging Keyword 1: dementia - Alzheimer's disease Keyword 2: cardiovascular disease Keyword 3: genetic disorders Objective: By age 40 years, adults with Down syndrome (DS) develop Alzheimer’s disease (AD) neuropathology and ~90% progress to dementia in their 50’s. Despite having few systemic vascular risk factors, individuals with DS have significant cerebrovascular disease that increases in severity with the clinical progression of AD, suggesting a vascular component of DS-AD that is not solely attributable to vascular risk factors. In the current study, we examined pathways that may link cerebrovascular disease to AD pathophysiology in adults with DS by testing the association among markers of cerebrovascular disease, inflammation/astrocytosis, and blood-based AD biomarkers across clinical AD diagnostic groups. Participants and Methods: One hundred eighty-five participants from the Alzheimer Biomarkers Consortium – Down Syndrome (mean age[SD]=45.2[9.3] years) with available MRI and plasma biomarker data were included in the study. Whole-brain white matter hyperintensity (WMH) volumes were derived from T2-weighted FLAIR MRI scans as a marker of small vessel cerebrovascular disease, and plasma Aβ42/Aβ40, p-tau217, GFAP, and neurofilament light (NfL) concentrations were measured with SIMOA assays, reflecting the amyloid, tau, inflammatory, and neurodegenerative pathophysiology, respectively implicated in AD. After examining bivariate relationships between WMH volume and plasma biomarker concentrations using Pearson correlation tests, we conducted a series of path analyses to examine potential causal pathways that may link cerebrovascular disease with AD pathophysiology in the total sample and in groups stratified by clinical diagnosis (i.e., cognitively stable, mild cognitive impairment [MCI], and clinical AD). Results: Larger WMH volume was associated with higher p-tau217 (r=0.376 [0.245, 0.494], p<0.0001), GFAP (r=0.253 [0.113, 0.383], p<0.001), and NfL (r=0.314 [0.178, 0.438], p<0.0001), but not with Aβ concentrations (r=-0.063 [-0.205, 0.082], p=0.398). Path analyses showed both a direct effect of WMH and an indirect effect through GFAP on p-tau217 concentrations, which, in turn, were associated with NfL concentrations in the total sample. Among cognitively stable participants, there was a direct and indirect effect through GFAP of WMH on p-tau217 concentrations, but p-tau217 concentrations were not associated with NfL concentrations. Among those with MCI, increased WMH volume had a direct positive effect on p-tau217 and NfL, but not on GFAP concentrations. GFAP concentrations had an indirect effect on NfL concentrations through p-tau217. Finally, in those diagnosed with dementia, there were no direct or indirect effects of WMH on plasma biomarker concentrations, but GFAP continued to have a positive indirect effect on NfL through p-tau217. Conclusions: Our findings show codependency and suggest a causal relationship between cerebrovascular disease and the progression of AD pathophysiology across clinical disease states in adults with DS. They suggest that cerebrovascular disease may promote AD-related neurodegeneration by increasing inflammation/astrocytosis and tau pathophysiology in pathways separate from Aβ, particularly in the presymptomatic and early phases of AD.

Poster

02/15/2024
09:30 am - 10:40 am
Room: Shubert Complex (Posters 1-60)

Poster Session 03: Neurotrauma | Neurovascular

Final Abstract #20

Vascular disease drives Alzheimer’s disease biomarker concentrations in adults with Down syndrome

Natalie Edwards, Columbia University, New York, United States
Patrick Lao, Columbia University, New York, United States
Olivia Ericsson, Columbia University, New York, United States
Mohamad Alshikho, Columbia University, New York, United States
Batool Rizvi, University of California, Irvine, Irvine, United States
Lisi Flores Aguilar, University of California, Irvine, Irvine, United States
Melissa Petersen, University of North Texas, Fort Worth, United States
Sid O'Bryant, University of North Texas, Fort Worth, United States
Dana Tudorascu, University of Pittsburgh, Pittsburgh, United States
José Gutierrez, Columbia University, New York, United States
Donna Wilcock, Indiana University, Indianapolis, United States
Elizabeth Head, University of California, Irvine, Irvine, United States
Adam Brickman, Columbia University, New York, United States

Category: Neuroimaging

Keyword 1: dementia - Alzheimer's disease
Keyword 2: cardiovascular disease
Keyword 3: genetic disorders

Objective:

By age 40 years, adults with Down syndrome (DS) develop Alzheimer’s disease (AD) neuropathology and ~90% progress to dementia in their 50’s. Despite having few systemic vascular risk factors, individuals with DS have significant cerebrovascular disease that increases in severity with the clinical progression of AD, suggesting a vascular component of DS-AD that is not solely attributable to vascular risk factors. In the current study, we examined pathways that may link cerebrovascular disease to AD pathophysiology in adults with DS by testing the association among markers of cerebrovascular disease, inflammation/astrocytosis, and blood-based AD biomarkers across clinical AD diagnostic groups.

Participants and Methods:

One hundred eighty-five participants from the Alzheimer Biomarkers Consortium – Down Syndrome (mean age[SD]=45.2[9.3] years) with available MRI and plasma biomarker data were included in the study. Whole-brain white matter hyperintensity (WMH) volumes were derived from T2-weighted FLAIR MRI scans as a marker of small vessel cerebrovascular disease, and plasma Aβ42/Aβ40, p-tau217, GFAP, and neurofilament light (NfL) concentrations were measured with SIMOA assays, reflecting the amyloid, tau, inflammatory, and neurodegenerative pathophysiology, respectively implicated in AD. After examining bivariate relationships between WMH volume and plasma biomarker concentrations using Pearson correlation tests, we conducted a series of path analyses to examine potential causal pathways that may link cerebrovascular disease with AD pathophysiology in the total sample and in groups stratified by clinical diagnosis (i.e., cognitively stable, mild cognitive impairment [MCI], and clinical AD).

Results:

Larger WMH volume was associated with higher p-tau217 (r=0.376 [0.245, 0.494], p<0.0001), GFAP (r=0.253 [0.113, 0.383], p<0.001), and NfL (r=0.314 [0.178, 0.438], p<0.0001), but not with Aβ concentrations (r=-0.063 [-0.205, 0.082], p=0.398). Path analyses showed both a direct effect of WMH and an indirect effect through GFAP on p-tau217 concentrations, which, in turn, were associated with NfL concentrations in the total sample. Among cognitively stable participants, there was a direct and indirect effect through GFAP of WMH on p-tau217 concentrations, but p-tau217 concentrations were not associated with NfL concentrations. Among those with MCI, increased WMH volume had a direct positive effect on p-tau217 and NfL, but not on GFAP concentrations. GFAP concentrations had an indirect effect on NfL concentrations through p-tau217. Finally, in those diagnosed with dementia, there were no direct or indirect effects of WMH on plasma biomarker concentrations, but GFAP continued to have a positive indirect effect on NfL through p-tau217.

Conclusions:

Our findings show codependency and suggest a causal relationship between cerebrovascular disease and the progression of AD pathophysiology across clinical disease states in adults with DS. They suggest that cerebrovascular disease may promote AD-related neurodegeneration by increasing inflammation/astrocytosis and tau pathophysiology in pathways separate from Aβ, particularly in the presymptomatic and early phases of AD.