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Influence of APOE Genotype on the neurodegenerative sequelae of repetitive mild TBI in an hTau mouse model.

Award Number: R56NS112166
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2020

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Influence of APOE Genotype on the neurodegenerative sequelae of repetitive mild TBI in an hTau mouse model. - Traumatic brain injury (TBI), often referred to as the “silent epidemic,” is widely discussed in the news today. The military loses thousands of man-years in experience due to the effects of TBI in soldiers, including those prematurely returned to active duty, as well as soldiers who cannot return to service. In the civilian population, closed head or concussive injury is also one of the leading causes of death and disability. Many young adults never regain premorbid skills or responsibilities after TBI despite intensive and comprehensive rehabilitation efforts on their behalf. The sequelae of TBI are a mixture of cognitive psychomotor and emotional (psychiatric) signs and symptoms, and the emotional and psychological burden on patients and caregivers can be enormous. Mild TBI (mTBI) accounts for the majority of all TBI cases and the devastating neurodegenerative outcomes of repetitive mild TBI (r-mTBI) have emerged over the last few years. The negative sequelae of r-mTBI pathogenesis will often already be well underway by the time interventions are sought, and there are currently no effective treatments. There is a clear need for improved and increased modeling of mTBI in the laboratory, to enable the dissection and evaluation of r-mTBI-dependent molecular responses and identification of better approaches to mitigate the negative outcomes. We have developed several different mouse models of repetitive mild TBI, with different neurobehavioral, neuropathological and biochemical outcomes. They recapitulate features of human TBI and are thus of relevance to a translational platform. We now propose to increase the translational relevance of our model by working with mice expressing both human Tau and apoE proteins (hTau/APOE mice), both of which have been demonstrated to significantly influence TBI pathogenesis. APOE genotype, a known risk factor for Alzheimer's Disease, has long been discussed as a risk factor for poor outcome after TBI. In addition to characterizing the new model we propose hypothesis-driven investigations of three mechanisms which our preliminary data, and published research, suggest as the means (individually or interactively) through which APOE genotype contributes to TBI outcome – specifically neuroinflammation, lipid dysregulation and clearance of tau from the brain. This work will reveal particular molecular pathways as therapeutic targets for r-mTBI drug discovery, and owing to the discoveries being made in the hTau/APOE model. we expect these results to be of more translational relevance and value to the TBI patient population.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	ROSKAMP INSTITUTE INC, THE	2040 WHITFIELD AVE	SARASOTA	FL	34243	MANATEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/21/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $492,853 )
2019	2019	ROSKAMP INSTITUTE INC, THE	2040 WHITFIELD AVE	SARASOTA	FL	34243	MANATEE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/31/2019	NEW	$492,853
														Subtotal = $492,853

Grand Total All Awards = $492,853

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Influence of APOE Genotype on the neurodegenerative sequelae of repetitive mild TBI in an hTau mouse model.

Award Number: R56NS112166

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2020

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