Project Grant RF1AG085887
- This $4.49 million project grant from the National Institutes of Health's National Institute on Aging will fund research at The Washington University to investigate the relationship between amyloid plaque deposition, cellular metabolic dysfunction, and functional brain organization in Alzheimer's disease (AD) mice models. Over three years, the researchers will use multi-photon fluorescence lifetime imaging microscopy, multi-parametric photoacoustic microscopy, and wide-field optical imaging to...
- The University of North Carolina at Chapel Hill (UNC-CH) received a $427,625 Project Grant award from the National Institute on Aging under the Aging Research program (CFDA 93.866) to develop and validate a computational framework for identifying excitation-inhibition imbalances in Alzheimer's disease (AD) using multi-modal neuroimaging data. The goal is to create an innovative technique that can noninvasively detect circuit-level disruptions in brain networks associated with AD pathology, which...
- The National Institute on Aging (NIA) awarded a $429,000 Project Grant (CFDA 93.866 - Aging Research) to Northeast Ohio Medical University (Neomed) to evaluate the role of acetylation on brain proteome dynamics in a mouse model of Alzheimer's Disease (AD) and type 2 diabetes mellitus (T2DM). The 2-year project aims to quantify proteome and acetylome dynamics in the hippocampus and frontal cortex of diet-induced diabetic and non-diabetic AD mice to determine the effect of T2DM-related...
- The federal Project Grant award from the National Institute on Aging (NIA), under the Aging Research program (CFDA 93.866), provides $426,674 to the University of North Carolina at Chapel Hill to investigate the "Implications of Long-Range Mossy Cell Signaling and Connectivity in Alzheimer's Disease (AD)". The 2-year project, starting on September 1, 2025, aims to identify changes in the activity of glutamatergic mossy cells in the dentate gyrus of the hippocampus and their impact on...
- This federal Project Grant award of $3,221,450.00 from the National Institute on Aging (CFDA 93.866 Aging Research) supports research to define how neuronal hyperexcitability in the retrosplenial cortex (RSC) contributes to the development of Alzheimer's disease (AD)-related behavioral deficits in mouse models. The research aims to determine the effect of inhibiting RSC layer 5 cells on spatial memory and navigation, as well as when hyperexcitability emerges in these cells across different AD...
- This $3.61 million project grant from the National Institutes of Health's National Institute on Aging will fund research from July 2022 to June 2025 aimed at understanding and addressing neurovascular coupling dysfunction in Alzheimer's disease and Alzheimer's disease-related dementias. Specifically, the University of Colorado Denver will investigate the hypothesis that restoring neurovascular coupling can mitigate synaptic plasticity deterioration in the hippocampus and its behavioral...
- This federal Project Grant award of $307,000.00 from the National Institute on Aging (CFDA 93.866 - Aging Research) aims to conduct a single, highly powered study to identify memory processes that are most sensitive to the asymptomatic, preclinical stage of Alzheimer's disease (AD) pathology. The study combines a continuous report item-location associative memory task with advanced behavioral and neural modeling to estimate subtle changes in memory precision that may differentiate healthy...
- This Project Grant award from the National Institute on Aging (NIA) under the Aging Research program (CFDA 93.866) provides $1,853,477 to the Research Foundation for Mental Hygiene, Inc. (RFMH) at the Nathan S. Kline Institute to conduct research on hyperexcitability and interictal spike activity in Alzheimer's disease. The research aims to investigate the origins and mechanisms of these neural phenomena, as well as evaluate whether selectively inhibiting them can improve cognition and reduce...
- This Project Grant award from the National Institutes of Health's Aging Research program (CFDA 93.866) will support research to identify early transcriptional and pathological changes in brain regions vulnerable to Alzheimer's disease (AD). The $459,076 award, granted to Trustees of Boston University, will use single-nucleus RNA sequencing and targeted mass spectrometry to profile cell type-specific gene expression and tau/amyloid beta proteoforms in the transentorhinal cortex, entorhinal...
- This $2,683,965 Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program supports the development and optimization of an "all-human cellular system" or "brain-chip" to study the cellular mechanisms underlying vulnerability to Alzheimer's disease (AD). The grant enables researchers at Brigham & Women's Hospital Inc. to leverage...
DYSREGULATED FRONTAL-SENSORY NETWORK AND COGNITIVE CONTROL BY ALZHEIMER'S DISEASE PATHOLOGY - COGNITIVE DECLINE IS ONE OF FREQUENT CHALLENGES ACCOMPANYING ALZHEIMER'S DISEASE (AD). HOWEVER, LITTLE IS KNOWN ABOUT THE LINK BETWEEN AD PATHOLOGY AND NEURAL CIRCUIT MECHANISMS ESPECIALLY IN FRONTAL CORTEX ESSENTIAL FOR COGNITIVE CONTROL BEHAVIOR. AMYLOID-B (AB) ACCUMULATION HAS BEEN IMPLICATED AS AN UPSTREAM EVENT IN AD PATHOGENESIS. AB-INDUCED CHANGES IN SYNAPTIC FUNCTION IN EXPERIMENTAL MODELS OF AD PATHOLOGY SUGGEST THAT AB MAY AFFECT NEURAL CIRCUIT CONNECTIVITY ESSENTIAL FOR COGNITIVE CONTROL BEHAVIOR. IDENTIFICATION OF COGNITIVE CIRCUIT NETWORK VULNERABLE TO AB ACCUMULATION WOULD ALLOW MITIGATING COGNITIVE DEFICITS IN IN AD. THE GOAL OF THIS STUDY IS TO EXAMINE TO WHAT EXTENT A FRONTAL COGNITIVE CONTROL CIRCUIT AND ASSOCIATED NETWORK IS VULNERABLE TO EARLY AD PATHOLOGY. A RECENT STUDY IN MICE DEMONSTRATED THAT FRONTAL-SENSORY PROJECTIONS FROM ANTERIOR CINGULATE AREA (ACA) TO VISUAL CORTEX (VIS) (ACAVIS) PLAYS A CAUSAL ROLE IN COGNITIVE CONTROL BY IMPROVING ATTENTION ESPECIALLY AFTER ERRORS. IN THIS STUDY, WE WILL ANALYZE APP KNOCK-IN (KI) MICE, WHICH EXPRESSES MUTANT HUMAN APP UNDER THE ENDOGENOUS MOUSE PROMOTER WHILE AVOIDING OVEREXPRESSION-ASSOCIATED ARTIFACTS, AND TEST A HYPOTHESIS THAT AD-RELATED AMYLOID PATHOLOGY DISRUPTS TOP-DOWN FRONTAL-SENSORY PROJECTION (AIM1) AND FRONTAL CHOLINERGIC NEUROMODULATION (AIM2), AND THAT THE INTERACTION BETWEEN THESE SYSTEMS CONTRIBUTES TO COGNITIVE CONTROL DEFICIT (AIM3). TO TEST THIS HYPOTHESIS, WE WILL APPLY CIRCUIT SPECIFIC APPROACHES TO MONITOR AND MANIPULATE NEURAL ACTIVITY IN ACAVIS PROJECTION NEURONS AND BASAL FOREBRAIN CHOLINERGIC NEURONS DURING FREE MOVING COGNITIVE CONTROL TASK USING FIVE CHOICE SERIAL REACTION TIME TASK IN APP KI MICE.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $2.0m | 5/31/24 |