IDENTIFYING THE MECHANISTIC ROLE OF AND REVERSING ABERRANT NEURAL ACTIVITY IN ALZHEIMER'S DISEASE - PROJECT…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
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ASST_NON_R00AG080110_075 · UNIVERSITY OF TEXAS AT AUSTIN · Department of Health and Human Services
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- Assistance award identifier
- ASST_NON_R00AG080110_075
- FAIN
- R00AG080110
- Recipient
- UNIVERSITY OF TEXAS AT AUSTIN
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $249,000
- Period
- Aug 16, 2023 – Aug 31, 2029
- Fiscal year
- 2026
- Place of performance state
- TX
- Source file
- FY2026_All_Assistance_Full_20261006.zip
Description
IDENTIFYING THE MECHANISTIC ROLE OF AND REVERSING ABERRANT NEURAL ACTIVITY IN ALZHEIMER'S DISEASE - PROJECT SUMMARY/ABSTRACT ALZHEIMERâS DISEASE (AD) IS A DEVASTATING DISEASE WITH ENORMOUS UNMET MEDICAL NEED. IT IS LIKELY NECESSARY TO UNDERSTAND, DETECT, AND TREAT ALZHEIMERâS DISEASE EARLIER IN DISEASE DEVELOPMENT. PATIENTS OFTEN EXHIBIT ABERRANT NEURAL ACTIVITY EVEN BEFORE PATHOLOGY OR COGNITIVE DECLINE. AMYLOID-BETA (AB) AND TAU CAN PERTURB NEURAL ACTIVITY, AND ACTIVITY CAN AFFECT THEIR LEVELS, THUS ABERRANT NEURAL ACTIVITY MAY BE BOTH A SYMPTOM AND CAUSE OF AB AND TAU, FORMING A VICIOUS CYCLE. THIS PROJECT WILL INVESTIGATE THE HYPOTHESIS THAT ABERRANT NEURAL ACTIVITY IS A PRIMARY DRIVER OF AND TRACTABLE THERAPEUTIC TARGET FOR ALZHEIMERâS DISEASE, AND THAT TARGETING IT CAN RESCUE COGNITIVE DEFICITS. THERE IS A LACK OF DIRECT EVIDENCE ON THE CAUSATIVE ROLE OF ABERRANT NEURAL ACTIVITY IN ALZHEIMERâS DISEASE, LET ALONE THE MECHANISMS, A SIGNIFICANT GAP IN OUR UNDERSTANDING. HUMAN IMAGING METHODS HAVE LOW RESOLUTION, AND HUMAN STUDIES CANNOT USE PRECISE PERTURBATIONS TO TEST DIRECT CAUSE AND EFFECT. YET, STIMULATION THERAPIES ARE USED ON PATIENTS, USING LIMITED DATA TO INFORM PROTOCOLS, RESULTING IN PROMISING BUT INCONCLUSIVE RESULTS. THIS PROJECT WILL USE CUTTING-EDGE SYSTEMS NEUROSCIENCE TECHNIQUES TO CONDUCT SINGLE-CELL RESOLUTION EXAMINATION AND PERTURBATION OF THE BRAIN TO DETERMINE THE MECHANISTIC ROLE OF ABERRANT NEURAL ACTIVITY IN COGNITIVE DECLINE IN ALZHEIMERâS DISEASE MICE, AND TO REVERSE IT. TO IDENTIFY ABERRANT SINGLE-NEURON AND NETWORK DYNAMICS, 2-PHOTON CA2+ IMAGING WILL BE USED IN ALZHEIMERâS DISEASE MICE DURING COGNITIVE TASKS OVER DISEASE PROGRESSION. THIS WILL BE THE FIRST LONGITUDINAL STUDY OF SINGLE-NEURON ACTIVITY IN ALZHEIMERâS DISEASE MICE DURING COGNITIVE TASKS, AND THE FIRST LIFELONG STUDY OF NEURAL ACTIVITY. TO DISCOVER ACTIVITY-BASED ANATOMICAL CONNECTIVITY CHANGES, ACTIVITY- DEPENDENT NEURON PROJECTION LABELING WILL BE USED T