Abstract Details

Title miRNA from Exosomes in Older Adults that have Asymptomatic White Matter Hyperintensities Suggest Role for Brain Inflammation in Precursor Stage to Cognitive Impairment

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P5 - Poster Session 5 (8:00 AM-9:00 AM)

Poster/Presentation
Number 10-005

Objective Here, we used the pattern and volume of white matter hyperintensity (WHI) detected on advanced magnetic resonance imaging (MRI) with exosomal miRNA to identify biologic processes associated with region specific WHI that occurs prior to the onset of vascular cognitive impairment (VCI).

Background The prevalence of WHI increases with aging, but not all patients that have WHI are clinically symptomatic, and the distribution of WHI can vary between patients. WHI are thought to be secondary to small vessel disease, but the pathophysiology may not be uniform in all brain regions. We hypothesize that inflammatory pathways will be key upstream mediators associated with WHI in patients with higher proportions of WHI in Alzheimer’s signature regions.

Design/Methods

Consent was obtained from Caucasian adults without VCI. Pipeline post-processing of T1- and T2-weighted sequences acquired on 3T-MRI was conducted using FreeSurfer. WHI ratio = percent of summated WHI normalized to intracranial volume from Alzheimer’s signature regions (parahippocampal gyrus, entorhinal cortex, inferior parietal lobule, precuneus, and cuneus) / total WHI volume normalized to intracranial volume - Alzheimer’s signature regions. RNA was extracted from exosomes isolated using exoRNeasy kit (Qiagen) from serum. Ion Proton System was used for RNA sequencing (Fisher). Partek Genomic Suite was used to select genes significantly associated with WHI ratio after correction for age and gender using ANCOVA modeling. Pathway analysis was performed using IPA ingenuity.

Results Of the 70 patients, 57% were woman, and the median age was 74 [interquartile range 66 to 79]. Seven miRNA (hsa-miR-33a; hsa-miR-376a; hsa-miR-38, hsa-miR-495, hsa-miR-656, hsa-miR-411) were significantly associated with WHI ratio. IPA ingenuity analysis identified 2 network functions, inflammatory response to neurological disease, and energy production/lipid metabolism.

Conclusions

These result suggest that neuroinflammation associated with aging may be an early key mediator of development of WHI, particularly when the distribution of the WHI is predominately in Alzheimer’s associated locations.

Authors/Disclosures
Alexis N. Simpkins, MD, PhD, MSCR, FAHA, FANA, FAAN (Cedars-Sinai Medical Center, Dept of Neurology) PRESENTER	Dr. Simpkins has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for National Institute of Neurological Disorders and Stroke Data Safety Monitoring Board. Dr. Simpkins has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Stroke: Vascular and Interventional Neurology. The institution of Dr. Simpkins has received research support from NIH/NIA. The institution of Dr. Simpkins has received research support from Bristol-Meyer Squibb Foundation. The institution of Dr. Simpkins has received research support from Corxel. Dr. Simpkins has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Thomas E. Foster, MD	No disclosure on file
	No disclosure on file
	No disclosure on file

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