RF1NS144213

SARS-COV-2 INITIATION AND ACCELERATION OF AD PATHOLOGY IN THE SETTING OF ENDOGENOUS AND EXOGENOUS RISK FACTORS - THE UNCERTAIN E,OLOGY OF ALZHEIMER’S DISEASE POSES SIGNIFICANT OBSTACLES TO THE DEVELOPMENT OF BOTH THERAPEU,C AND PREVEN,ON STRATEGIES. AT THE ROOT OF THIS QUANDARY IS THE FACT THAT FAMILIAL DISEASE ACCOUNTS FOR A VERY SMALL FRAC,ON OF CASES, WITH THE VAST MAJORITY REMAINING GENE,CALLY SPORADIC. THE MOST WIDELY KNOWN RISK FACTOR, THE APOE4 ALLELE OF THE GENE CODING FOR APOLIPOPROTEIN E, HAS BEEN IDEN,FIED, BUT MECHANIS,C ,ES TO DISEASE DEVELOPMENT ARE S,LL EMERGING. NEUROINFLAMMA,ON HAS LONG BEEN SUSPECTED AS A CONTRIBU,NG FACTOR, AND REGULAR EXERCISE DOCUMENTED AS A MI,GA,NG FACTOR, WITH THEORIES TO EXPLAIN THEIR EFFECTS BEING POSED, BUT AGAIN WITH LIGLE MECHANIS,C PROOF. A PICTURE OF A VERY COMPLEX PROCESS OF INI,A,ON AND PROGRESSION OF ALZHEIMERS DISEASE AND RELATED DEMEN,AS (AD/RD) INCLUDING PICK’S DISEASE, FRONTO-TEMPORAL DEMEN,A (FTD) AND OTHER TAUOPATHIES, IS SLOWLY EMERGING. A KEY FACTOR IN THE E,OLOGY OF AD/RD THAT REPEATEDLY CROPS UP IS VIRAL INFEC,ON. COVID-19 HAS BROUGHT NEW AGEN,ON TO THIS FACTOR, WITH THE OBSERVA,ON THAT A FRAC,ON OF THOSE INFECTED EXPERIENCE “BRAIN-FOG”, A CATCH-ALL TERM THAT INCLUDES COGNI,VE DYSFUNC,ON, MEMORY DYSFUNC,ON AND MENTAL FA,GUE, MARKED BY IMPAIRED ABILITY TO PERFORM MENTAL TASKS COMPARED TO BEFORE THE INFEC,ON. SEVERAL FACTORS HOWEVER, COMPLICATE AN UNDERSTANDING OF THE EFFECT OF COVID-19 ON AD/RD AND CONS%TUTE THE DRIVING QUES%ONS FOR THIS PROPOSAL: THESE INCLUDE (1) WHAT ARE THE RELA,VE CONTRIBU,ONS OF GENE,C RISK FACTORS AND COVID-19 ON INI,A,ON AND PROGRESSION OF AD/RD? (2) WHAT ARE THE EFFECTS OF SARS-COV-2 VARIANTS: EX,NCT STRAINS E.G. WUHAN, ALPHA, DELTA VS. CURRENT STRAINS E.G. OMICRON AND ITS LINEAGE, AND THEIR SEQUEN,AL INFEC,ON ON AD/RD INI,A,ON AND PROGRESSION? (3) WHAT ARE THE EFFECTS OF PRIOR INFEC,ONS WITH OTHER HIGHLY PREVALENT VIRUSES E.G. HSV-1 ON THE INI,A,ON AND PROGRESSION OF AD/RD BY SARS-COV-2? SUCCESSFUL COMPLE,ON OF THIS WORK WILL PROBE THE RELA,ONSHIP BETWEEN COVID-19 AND NEURODEGENERA,ON, WHILE YIELDING DEEP MECHANIS,C INSIGHTS INTO THE ROLE OF SARS-COV-2 IN COMBINA,ON WITH HSV-1 IN TRIGGERING/ACCELERA,NG AN AD PHENOTYPE AND FOCUS A SEARCH FOR THERAPEU,C TARGETS TO COUNTERACT AD INI,A,ON/ACCELERA,ON/PROGRESSION.

Baylor College Of Medicine

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

National Institute on Aging (NIA) [HHS - NIH]

Texas United States

State-Wide

Neuropathological Interactions Between COVID-19 and ADRD (R01 - Clinical Trial Not Allowed) (PAR-24-203)