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Grants > Improving Cognitive Function in AD Therapy Using a Combinatorial Approach of Reducing Disease Progression and Increasing Memory Updated On: Feb. 2, 2025
Alzheimer's Disease Research Grant

Improving Cognitive Function in AD Therapy Using a Combinatorial Approach of Reducing Disease Progression and Increasing Memory

a headshot of Brati Das, PhD

Principal Investigator

Brati Das, PhD

University of Connecticut Health Center

Farmington, CT, USA

About the Research Project

Program

Alzheimer's Disease Research

Award Type

Postdoctoral Fellowship

Award Amount

$200,000

Active Dates

September 01, 2020 - November 30, 2022

Grant ID

A20201729F

Mentor(s)

Riqiang Yan, PhD, The Cleveland Clinic Foundation

Goals

Aβ is the main component of amyloid plaques found in the brains of Alzheimer patients. Production of Aβ is nearly stopped by inhibiting BACE1 enzyme. Therefore, BACE1 inhibitors are used to reduce Aβ production and amyloid deposition. But their use can lead to many side effects that impact learning and storage of memory. Therefore, it is critical to develop new therapeutic strategies. We propose to use BACE1 inhibitor drugs in combination with mGluR activator drugs. This combination therapy will stop the disease progression and help in memory retention at the same time. We will test our strategy in mice in the current study. Positive results from this study will provide Alzheimer patients a better quality of life.

Summary

Abnormal circulation of Abeta peptides in brain likely causes Alzheimer’s disease. Inhibition of BACE1, the enzyme that initiates Abeta production, is therefore being explored to treat AD patients. However clinically tested BACE1 inhibitors have failed to improve cognitive function despite strong reduction in Abeta generation. We observe BACE1 activity is essential for synaptic functions and ultimately cognitive abilities. Therefore, we explore molecular targets which can reverse synaptic impairments. One such candidate is mGluR PAM. We are developing treatment therapies combining BACE1 inhibitors for reducing amyloid deposition and mGluR PAM for countering synaptic deficits as a more effective approach for treating AD patients.