Abstract Details

Title Identification and Preliminary Validation of a Plasma Profile Associated with Cognitive Decline in Dementia and At-risk Individuals: A Retrospective Cohort Analysis

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-029

Objective

To evaluate a plasma signature of amyloid, metallo-proteinases (MMPs), and inflammatory markers in a cohort of at-risk individuals and individuals diagnosed with probable Alzheimer’s disease (pAD).

Background Biomarker discovery is a major need for earlier dementia diagnosis. We recently found that a plasma-based measure of amyloid (Aβ₄₀, Aβ₄₂) and inflammatory molecules (IL-8, TNF-α) predicted cognitive deterioration in an AD-asymptomatic Down syndrome population, with the pre-dementia stage partly characterized by upregulation of MMPs and pro-inflammatory cytokines (TNF-α, IL-6, IL-10).

Design/Methods

Using multiplex arrays, we measured Aβ₄₀, Aβ₄₂, MMP-1, MMP-3, MMP-9, IFN-γ, TNF-α, IL-6, IL-8, and IL-10 in plasma from 107 individuals followed every 6-months for 3-years. Final diagnoses included: pAD (n=28), mild cognitive impairment (MCI, n=30), subjective memory impairment (SMI, n=30), and asymptomatic (NCI, n=19). Blood was drawn at final follow-up. We used linear and logistic regressions to examine biomarker associations with prior known decline on the Montreal Cognitive Assessment (MoCA) and the Cambridge Cognitive Examination (CAMCOG); as well as disease progression by the time of blood-draw. We derived a biomarker composite from the individual markers, and tested its association with a clinical diagnosis of pAD.

Results Lower Aβ₄₀ and Aβ₄₂ and higher IL-8, IL-10 and TNF-α were associated with greater cognitive decline per the MoCA and CAMCOG. MMP-3 was higher in SMI, MCI, and pAD than NCI (p=0.02). Whereas the other investigative molecules did not differ between groups, composite scores – created using MoCA/CAMCOG-based trends in Aβ₄₀, Aβ₄₂, MMP-1, MMP-3, IL-8, IL-10 and TNF-α – were associated with a final diagnosis of pAD (c-statistic 0.732, 95%CI 0.614-0.849 vs. 0.602, 95%CI 0.477-0.747 for age-sex alone).

Conclusions Plasma amyloid, MMP, and inflammatory biomarkers demonstrated differences in individuals with cognitive deterioration and/or progression to MCI/pAD. Our findings support studying these markers earlier in the continuum of probable AD as well as in specific dementias.

Authors/Disclosures
PRESENTER	No disclosure on file
Aravind Ganesh, MD (Department of Clinical Neurosciences, University of Calgary)	Dr. Ganesh has received personal compensation in the range of $0-$499 for serving as a Consultant for Figure 1. Dr. Ganesh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier Canada. Dr. Ganesh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Ganesh has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli-Lilly. Dr. Ganesh has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Let's Get Proof (Collavidence Inc). Dr. Ganesh has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for ��ɫ�� (journals Neurology and Neurology: Clinical Practice). Dr. Ganesh has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association (journal: Stroke). Dr. Ganesh has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers (for Frontiers in Neurology). Dr. Ganesh has or had stock in SnapDx.Dr. Ganesh has or had stock in Collavidence Inc.Dr. Ganesh has or had stock in DataSimpl. The institution of Dr. Ganesh has received research support from Canadian Institutes of Health Research . The institution of Dr. Ganesh has received research support from Alberta Innovates. The institution of Dr. Ganesh has received research support from University of Calgary Centre for Clinical Research. The institution of Dr. Ganesh has received research support from Innovation 4 Health. The institution of Dr. Ganesh has received research support from Government of Canada INOVAIT. The institution of Dr. Ganesh has received research support from Campus Alberta Neuroscience. The institution of Dr. Ganesh has received research support from Alzheimer Society of Canada. The institution of Dr. Ganesh has received research support from Heart and Stroke Foundation of Canada. The institution of Dr. Ganesh has received research support from New Frontiers in Research Fund. The institution of Dr. Ganesh has received research support from Panmure House. The institution of Dr. Ganesh has received research support from Brain Canada. The institution of Dr. Ganesh has received research support from MSI Foundation. The institution of Dr. Ganesh has received research support from France Canada Research Fund. Dr. Ganesh has received intellectual property interests from a discovery or technology relating to health care.
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