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Background <p>Neurovascular biomarkers have the potential to enhance early diagnosis of Alzheimer’s disease (AD) and AD-related dementias (ADRD), as cerebrovascular alterations often precede neurodegeneration. However, their clinical application remains challenging due to insufficient specificity, heterogeneity, and technical limitations.</p> Methods <p>Here, we report that vessel- and cortical layer-specific parameters exhibit promising diagnostic sensitivity for neurovascular impairments in an AD/ADRD mouse model, apolipoprotein E (<i>APOE</i>) 4 knock-in (KI), compared to <i>APOE3</i>-KI at 12 months of age. Using two in vivo imaging modalities, 3D capillary-resolution optical Doppler tomography and laser speckle contrast imaging, we measured 36 morphological and functional vascular parameters and evaluated their diagnostic performance using a machine-learning Support Vector Machine classifier.</p> Results <p><i>APOE4</i> mice showed significant alterations including reduced venular and arterial cerebral blood flow velocities and diameters, increased vascular tortuosity, layer-dependent decreases in vascular density, and impaired cerebrovascular reactivity. Venule- and microcirculation-related parameters and dynamic vasoactivity to brain stimuli demonstrated high diagnostic accuracy (~ 90%).</p> Conclusion <p>Together, these findings provide in vivo evidence for early, cortical layer-specific neurovascular dysfunction caused by <i>APOE4</i> that increases the susceptibility to dementia and highlight the potential of combining neurovascular biomarkers from optical imaging with AI-based classifier for identification of increased AD/ADRD risk.</p>

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Cortical layer multi-parameter analysis of neurovascular impairments in AD/ADRD rodent model with in vivo optical imaging

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月22日

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  • Hyomin Jeong,
  • Jiaxiang Ren,
  • Wensheng Cheng,
  • Nora D. Volkow,
  • Haibin Ling,
  • Donghui Zhu,
  • Congwu Du,
  • Yingtian Pan

摘要

Background

Neurovascular biomarkers have the potential to enhance early diagnosis of Alzheimer’s disease (AD) and AD-related dementias (ADRD), as cerebrovascular alterations often precede neurodegeneration. However, their clinical application remains challenging due to insufficient specificity, heterogeneity, and technical limitations.

Methods

Here, we report that vessel- and cortical layer-specific parameters exhibit promising diagnostic sensitivity for neurovascular impairments in an AD/ADRD mouse model, apolipoprotein E (APOE) 4 knock-in (KI), compared to APOE3-KI at 12 months of age. Using two in vivo imaging modalities, 3D capillary-resolution optical Doppler tomography and laser speckle contrast imaging, we measured 36 morphological and functional vascular parameters and evaluated their diagnostic performance using a machine-learning Support Vector Machine classifier.

Results

APOE4 mice showed significant alterations including reduced venular and arterial cerebral blood flow velocities and diameters, increased vascular tortuosity, layer-dependent decreases in vascular density, and impaired cerebrovascular reactivity. Venule- and microcirculation-related parameters and dynamic vasoactivity to brain stimuli demonstrated high diagnostic accuracy (~ 90%).

Conclusion

Together, these findings provide in vivo evidence for early, cortical layer-specific neurovascular dysfunction caused by APOE4 that increases the susceptibility to dementia and highlight the potential of combining neurovascular biomarkers from optical imaging with AI-based classifier for identification of increased AD/ADRD risk.