Senile plaques in Alzheimer’s disease are primarily induced by cerebral vessel leakage of red blood cells and other blood contents

Senile plaque is one of the most prominent pathological hallmarks of Alzheimer’s disease (AD). However, the mechanism governing the generation of senile plaques remains a mystery. Many researchers believed that senile plaques are derived from neuronal cells, however, there is also strong evidence showing that senile plaques are linked with cerebral microhemorrhage. We analyzed the major neural markers, cerebral blood vessel and blood-related markers in AD brain sections with immunohistochemistry in conjunction with fluorescence imaging and TUNEL assay. We found few colocalizations between neural markers and senile plaque Aβ staining while abundant colocalizations between blood markers such as HBA and ApoE with senile plaque Aβ. Senile plaques also colocalized with a characteristic blue autofluorescence, which is prominently located in the blood stream and associated with red blood cells. Additionally, senile plaques did not colocalize with blood vessel marker Collagen IV. It appears that Aβ either directly leaks out of damaged blood vessel wall or is transported out of blood vessel through blood vessel microaneurysm. By staining of another marker of cerebral blood vessel LRP1, we could also observe that Aβ directly came out broken blood vessels at the center of dense-core plaques. In AD brain tissues, platelets were found along blood vessel walls and also in senile plaques, thus platelets likely also contribute to senile plaque formation. In summary, we concluded that senile plaques are primarily induced by cerebral vessel leakage of red blood cells and other blood contents.

Artery-on-a-chip platform for automated, multimodal assessment of cerebral blood vessel structure and function

We present a compact microfluidic platform for the automated, multimodal assessment of intact small blood vesselsin vitro.

Abstract 3802: Retinal Vasoreactivity as a Marker of Impaired Cerebral Function in Diabetes

The eye and the brain share embryological, anatomic and physiological similarities, which suggest that the retinal microvasculature may be an ideal surrogate marker of cerebrovascular function. This is intriguing, as the cerebral vasculature cannot be directly measured in a non-invasive manner. In epidemiological studies abnormal retinal Arteriovenous Ratios (AVR) are associated with an increased risk of stroke and cerebrovascular disease. However, the association between retinal vasoreactivity measurements and cerebral blood vessel function remains unknown. An attenuated retinal vasoreactivity may indicate endothelial dysfunction in the eye and brain and may prove to be useful as a marker of cerebrovascular disease in high risk populations such as in diabetics. STUDY GOALS: To examine 1) the impact of diabetes at different disease stages on measures of cerebrovascular function and 2) the relationship between retinal blood vessel reactivity, retinal AVRs and measures of cerebral small vessel function. METHODS: This cohort study included 29 type 2 diabetics, 14 pre-diabetics, and 14 healthy controls (ages: 37 to 75 years). Retinal vasoreactivity was measured with the Dynamic Vessel Analyzer (Imedos, Jena, Germany) following high frequency flicker light stimulation. Cerebrovascular blood flow velocity of the Middle Cerebral Artery (MCA) was assessed by Transcranial Doppler Ultrasound (TCD) (Siemens, USA). RESULTS: Progression of diabetes was found to be significantly associated with attenuation of light flicker stimulus response (P=0.0009 artery, P=0.0001 vein, CI 95%), AVR (P=0.0070, CI 95%), PI (P=0.0202, CI 95%), RI (P=0.0033, CI 95%) and hyperventilation-breath hold (P≤0.0001, CI 95%). Across all groups, attenuated retinal arterial and venous diameter responses to the light flicker stimulus were associated with an increase in MCA RI (P=0.02, r=-0.30 artery, P=0.06, r=-0.24 vein, CI 95%). An attenuated venous diameter response was associated with an increase in PI (P=0.02, r=-0.29 vein, CI 95%). In addition, attenuated retinal diameter responses were also associated with a decrease in MCA mean flow velocities following hyperventilation-breath hold (P=0.05, r=0.26 artery, P=0.01, r=0.34 vein, CI 95%). Attenuated retinal responses were also correlated with a reduction in AVR (P=0.05, r=0.26 artery, P=0.15, r=0.19 vein, CI 95%). CONCLUSION: Impairment of retinal vasoreactivity is associated with cerebrovascular dysfunction across the continuum of diabetes, possibly indicating that the eye reflects changes in cerebral blood vessel function and stroke risk.