# Inflammatory Networks Mediating Cognitive Decline In Preclinical Alzheimers Disease

> **NIH NIH K23** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $173,933

## Abstract

PROJECT SUMMARY/ABSTRACT
 Alzheimer's disease (AD) is a devastating neurodegenerative disease that causes progressive
cognitive decline towards dementia. One in nine people over 65 yrs of age in the US has AD and it is the fifth-
leading cause of death in this age group. The over 65 population is expected to double by 2050. Delineating
factors that predict and prevent cognitive decline related to AD are hugely important but are still poorly
understood.
 This Career Development Award will provide additional training and research opportunities in
bioinformatics and neuroinflammation for Dr. Pillai to advance his clinical research skills to address a current
knowledge gap in the role for inflammatory factors in AD progression. He is a behavioral neurologist
experienced in cognitive neuroscience research with a long-term goal to establish a programmatic body of
research using bioinformatics tools to delineate the molecular factors that underpin cognitive decline and
disease progression among neurodegenerative diseases.
 Knowledge of inflammatory factors that drive AD progression will be critical in designing novel
therapeutic strategies to prevent cognitive decline. This award will aid him in achieving these goals through a
structured training plan that includes formal course work in bioinformatics and statistical techniques, as well as
relevant laboratory and clinical research in the immunobiology of AD. He will also receive additional training in
grant writing and the design and administration of clinical trials research to facilitate his future focus on bringing
bioinformatics insights from large data to bear fruitful impact in the clinic.
 The research at the foundation of the current application is a clinical translational study that aims to
characterize the temporal course of neuroinflammation, blood brain barrier (BBB) integrity and
neurodegeneration in AD. Dr.Pillai's preliminary studies in this direction, funded by the Alzheimer Association,
suggest that there is a strong relationship between the above three domains, among AD patients at the stage
of mild cognitive impairment (MCI). The current award will help Dr.Pillai confirm and extend these insights
among healthy, cognitively intact elders who are APOE ε4 risk gene carriers, a significant percentage of whom
may be in the preclinical stage of AD. We hypothesize that higher levels of specific baseline cerebrospinal fluid
inflammatory markers and BBB break down markers correlate with higher levels of neurodegeneration and
impacts cognitive decline over 24 months among these subjects. We will confirm and validate the temporal
course of inflammatory protein changes with longitudinal multiplex biomarker and genome wide expression
changes over 24 months and against data from other large national data (Alzheimer's Disease Neuroimaging
Initiative, Accelerating Medicines Partnership-AD). This research will characterize individual propensities for
deleterious inflammatory responses that would be us...

## Key facts

- **NIH application ID:** 10162456
- **Project number:** 5K23AG055685-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** JAGAN AYYAPPAN PILLAI
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $173,933
- **Award type:** 5
- **Project period:** 2017-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162456

## Citation

> US National Institutes of Health, RePORTER application 10162456, Inflammatory Networks Mediating Cognitive Decline In Preclinical Alzheimers Disease (5K23AG055685-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10162456. Licensed CC0.

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