Super-Resolution Ultrasound Reveals Cerebrovascular Impairment in a Mouse Model of Alzheimer’s Disease

Matthew R. Lowerison, Nathiya Vaithiyalingam Chandra Sekaran, Zhijie Dong, Xi Chen, Qi You, Daniel A. Llano, Pengfei Song

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere1251232024
Pages (from-to)1-14
Number of pages14
JournalJournal of Endocrinology
Issue number9
StatePublished - Feb 2024


  • Alzheimer’s disease
  • cerebral blood flow
  • microbubble
  • mouse
  • super-resolution ultrasound

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism


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