Super-Resolution Ultrasound Reveals Cerebrovascular Impairment in a Mouse Model of Alzheimer's Disease
Increasing evidence has suggested a link between cerebrovascular disease and the cognitive impairment associated with Alzheimer's disease. However, detailed descriptions of microvascular changes across brain regions and how they relate to other more traditional pathology have been lacking. Addi...
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| Published in: | The Journal of neuroscience Vol. 44; no. 9; p. e1251232024 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Society for Neuroscience
28-02-2024
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Increasing evidence has suggested a link between cerebrovascular disease and the cognitive impairment associated with Alzheimer's disease. However, detailed descriptions of microvascular changes across brain regions and how they relate to other more traditional pathology have been lacking. Additionally, the efforts to elucidate the interplay between cerebral microvascular function and Alzheimer's disease progression are complicated by the necessity of probing deep-brain structures since early-stage Alzheimer's disease typically involves hippocampal pathology. The purpose of this study was to examine changes in microvascular dynamics in a mouse model of Alzheimer's disease using cohorts that were age-matched to wild-type controls. Data from both sexes were included in this study. Super-resolution ultrasound localization microscopy revealed microvascular functional and structural features throughout the whole brain depth to visualize and quantify. We found that functional decreases in hippocampal and entorhinal flow velocity preceded structural derangements in regional vascular density. Co-registered histological sectioning confirmed the regionalized perfusion deficits seen on ultrasound imaging, which were co-localized with amyloid beta plaque deposition. In addition to providing global vascular quantifications of deep brain structures with a high local resolution, this technology also permitted velocity-profile analysis of individual vessels and, in some cases, allowed for decoupling of arterial and venous flow contributions. These data suggest that microvascular pathology is an early and pervasive feature of Alzheimer's disease and may represent a novel therapeutic target for this disease. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: M.R.L., N.V.C.S., D.A.L., and P.S. designed research; M.R.L. and N.V.C.S. performed research; Z.D., X.C., and Q.Y. contributed unpublished reagents/analytic tools; M.R.L. and N.V.C.S. analyzed data; M.R.L., N.V.C.S., D.A.L., and P.S. wrote the paper. M.R.L. and N.V.C.S. contributed equally to this work. P.S. and M.R.L. have patents in the field of super-resolution ultrasound imaging, some of which have been licensed. This study was partially supported by the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, and the National Institute on Aging of the National Institutes of Health under Grants R21EB030072, R56NS131516, R21DC019473, R21AG077173, and R03AG059103, respectively, as well as a grant to D.A.L. from the Kiwanis Neuroscience Research Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. N.V.C.S. and M.R.L. are supported by Beckman Institute Postdoctoral Fellowships. |
| ISSN: | 0270-6474 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.1251-23.2024 |