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 ...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.展开更多
基金supported in part by National Institutes of Health(NIH)grants 2R01 DA029718(CD,YP),R01AG064798(D.Z.),R21DA042597(CD,YP,HL),R01AG064798(DZ)NIH’s Intramural Program of NIAAA(NDV).
文摘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.
