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A fiber implant for long-term, deep-brain imaging and manipulation in mouse models of Alzheimer disease

Award Number: R01AG095248
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2026
PERIOD OF PERFORMANCE END DATE: 12/31/2030

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A fiber implant for long-term, deep-brain imaging and manipulation in mouse models of Alzheimer disease - PROJECT SUMMARY Neurological disorders, such as Alzheimer disease (AD) and Parkinson disease, chronically affect critical regions of the deep brain, including the hippocampus and substantia nigra. Long-term monitoring of disease progression and responses to interventions in mouse models, which have well-characterized timelines and are equipped with a variety of manipulation tools, holds significant promise for uncovering new mechanisms and therapeutic targets. However, existing technologies, including optical microscopy and microendoscopy, face major limitations related to invasiveness, biocompatibility, and long-term accessibility when studying the deep brain in mouse models. To address these challenges, we propose the development of a fiber implant for longitudinal, multifunctional, deep- brain interfacing in awake mice. This implant, with a small diameter and constructed from biocompatible materials, has the potential to address the limitations of existing approaches and enable longitudinal deep-brain monitoring with minimal impact on brain function over an extended period (>9 months). Our innovative design will integrate photoacoustic microscopy (PAM) and two-photon microscopy (TPM) for simultaneous functional and molecular imaging, along with microelectrode-based neural stimulation and microfluidics-based drug delivery for targeted brain manipulation: creating a comprehensive bidirectional interface. We will use this technology to test a set of hypotheses derived from our prior study: (1) hippocampal-dependent memory loss is a consequence of impaired blood oxygen supply in the hippocampus; (2) reduced blood oxygen supply is secondary to vascular amyloid pathology; and (3) restoring blood oxygen supply rescues memory loss. Testing these hypotheses relies on the advanced capabilities of the bidirectional fiber implant. Specifically, longitudinal monitoring is essential to unravel the temporal relationship between amyloid pathology, vascular dysfunction, and memory loss in AD. Access to the hippocampus is critical, as it is one of the first regions affected in AD and is directly linked to memory loss. The simultaneous use of PAM and TPM will allow for comprehensive assessments of both blood oxygen supply and vascular amyloid pathology. Microelectrode-based stimulation will facilitate the evaluation of the impairment in vascular functional hyperemia, while microfluidic drug delivery will enable localized application of a vasodilator to determine whether blood oxygen supply can be restored in the face of amyloid pathology, and, if so, how such restoration affects memory function in AD. Successful completion of this project will enhance our capacity for longitudinal studies of the deep brain in animal models and provide new insights into the mechanisms underlying memory impairment in AD, with significant implications for developing therapeutic strategies targeting vascular dysfunction and oxygen supply restoration.


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: 2026 ( Subtotal = $683,028 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Aging Research	000	1	12/30/2025	NEW	$683,028
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Aging Research	001	1	1/14/2026	NEW	$0
														Subtotal = $683,028

Grand Total All Awards = $683,028

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A fiber implant for long-term, deep-brain imaging and manipulation in mouse models of Alzheimer disease

Award Number: R01AG095248

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2026

PERIOD OF PERFORMANCE END DATE: 12/31/2030

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