Administrative Supplement: Development of a vascular dementia model

  • Wilcock, Donna (PI)

Grants and Contracts Details


The parent RO1 is designed to study the co-morbidity of cerebrovascular disease / vascular dementia with the amyloid deposition of Alzheimer’s disease. The cerebrovascular disease model proposed was hyperhomocysteinemia. We have shown that hyperhomocysteinemia induces microhemorrhages in the cerebral cortex, neuroinflammation and cognitive deficits. We have now performed specific aim 1 of the RO1 and found that amyloid deposition shifts toward the vasculature, increasing cerebral amyloid angiopathy, while not affecting total Ab levels. Vascular dementia is a multi-faceted form of dementia, with multiple etiologies leading to the clinical phenotype of dementia. The most prevalent pathologies causing vascular dementia microinfarcts, lacunar infarcts and microhemorrhages. The hyperhomocysteinemia model demonstrates grey matter microhemorrhages, primarily cortical. A model that demonstrates white matter microinfarcts and lacunar infarcts is the bilateral carotid artery stenosis model (BCAS). The BCAS model was developed by Hidekazu Tomimoto’s research group in Kyoto, Japan. The model involves the placement of 0.18 internal diameter coils around the left and right common carotid artery. There have been numerous research studies from Tomimoto and colleagues detailing pathology and phenotype induced in this model. We propose to use the administrative supplement to establish the model in the laboratory and perform a detailed time-course of the cerebrovascular pathology induced in both wildtype and APP/PS1 transgenic mice. We will then compare and contrast these findings with the hyperhomocysteinemia model already published and established in the laboratory. The ability to study both the BCAS and hyperhomocysteinemia models in our laboratory will allow us to examine white matter versus grey matter cerebrovascular disease and the effects on Alzheimer’s disease pathology and cognitive outcomes over time.
Effective start/end date7/1/124/30/14


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