Abstract Details

Title An inflammatory marker panel provides insight into white matter abnormalities: the Northern Manhattan Study

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S34 - Aging and Dementia: Risk Factors, Biomarkers, and Neuropathology (1:33 PM-1:44 PM)

Poster/Presentation
Number 004

Background Risk factors for cerebral white matter disease include traditional vascular risk factors. Immune mechanisms in small vessel ischemic injury are less well-characterized.

Objective To determine whether immune protein panels correlate with presence of white matter abnormalities on brain magnetic resonance imaging (MRI).

Design/Methods A subsample of the prospective Northern Manhattan Study underwent brain MRI, and white matter hyperintensity volume (WMHV) was assessed quantitatively and adjusted for head circumference. Contemporaneous blood samples were analyzed using a customized, 60-plex, bead-based immunoassay (Affymetrix, Santa Clara, CA). We used LASSO procedures to select markers and their interactions independently associated with WHMV. We used linear regression models to assess cross-sectional associations of known correlates of WMHV (age, race/ethnicity, socioeconomic status, and vascular risk factors) with WMHV, and assessed model fit before and after addition of LASSO-selected immune markers and their interactions.

Results

RESULTS: Participants (n=1179) had mean age 70+8.9 years; 60% were women, and 68% Hispanic. Inclusion of LASSO-selected immune markers and their interactions improved model fit above other risk factors (p for likelihood ratio test<0.00001). Specific immune markers included in the final model were CXCL9, SCF, sFasL, serpin E1 (plasminogen activator inhibitor-1), TGF-α, VCAM1, CCL3, CCL5, and interleukins 5, 1a, and 31. The magnitude of effect of the interferon-γ induced, angiostatic CXCL9 (beta per standard deviation (SD)=0.047, p=0.09), and SCF (beta per SD=0.0403, p=0.1472), a growth factor implicated in microglial and neural progenitor responses to ischemic brain injury, were comparable to those of other risk factors, such as age (beta per year=0.0482, p<0.0001) and diastolic blood pressure (beta per 5 mm Hg=0.0405, p=0.0131).

Conclusions

Immune markers involved in distinct pathways associate with white matter disease in a multi-ethnic cohort. Further work is needed to determine how immune networks may cause white matter disease, and whether immunotherapies may counter these effects.

Authors/Disclosures
Mitchell S. Elkind, MD, MS, FAAN PRESENTER	Dr. Elkind has received personal compensation for serving as an employee of American Heart Association. Dr. Elkind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Atria Academy.
Yeseon Moon	No disclosure on file
Janet T. DeRosa	No disclosure on file
	No disclosure on file
Tatjana Rundek, MD, PhD	The institution of Dr. Rundek has received research support from NIH.
Clinton B. Wright, MD, FAAN (NINDS)	An immediate family member of Dr. Wright has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. An immediate family member of Dr. Wright has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MARSHALL DENNEHY. The institution of an immediate family member of Dr. Wright has received research support from Oncospace. Dr. Wright has received publishing royalties from a publication relating to health care. An immediate family member of Dr. Wright has received personal compensation in the range of $500-$4,999 for serving as a surveyor with ASTRO.
Ralph L. Sacco, MD, MS, FAHA	Dr. Sacco has received personal compensation in the range of $100,000-$499,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. The institution of Dr. Sacco has received research support from NIH, NINDS, NCATS, NIMHD. The institution of Dr. Sacco has received research support from FL Department of Health. Dr. Sacco has received research support from University of Washington, Seattle. Dr. Sacco has received publishing royalties from a publication relating to health care.
	No disclosure on file
Ken Cheung	No disclosure on file

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