ZULOAGA LAB
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​Research​

Our long-term goal is to determine how sex, aging, and sex hormones influence vascular and metabolic contributions to dementia and to develop sex-specific therapeutic strategies to improve cognitive function and reduce the burden of dementia.
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Current Projects:
1) Sex differences in effects of prediabetes on vascular contributions to cognitive impairment and dementia (VCID).
VCID is the second leading cause of dementia.  Diabetes impairs vascular function and is a major risk factor for VCID. Vascular effects of diabetes are greater in females than males, however, little is known regarding the effects of prediabetes.  We have found that prediabetes causes more severe cogntive impairment in females compared to males using a mouse model of VCID.  Currenlty we are determinig sex differences in the underlying neuro-, glial-, and vascular pathology. This project was funded by an American Heart Association Scientist Development Grant.

2) Metabolic & Hormonal Mechanisms of VCID.
Risk of VCID is significantly increased in metabolically impaired (prediabetic/diabetic) post-menopausal women. This study will determine if  menopause exacerbates the effects of prediabetes on VCID pathology and cognitive deficits.  Further, will be determine if these effects can be reversed by increasing estrogen specifically in the brain.  Our study will provide mechanistic insight that will facilitate future interventions to decrease the burden of dementia, particularly in the high-risk population of prediabetic post-menopausal women.  This project is funded by an R01 from NINDS. 

3) Sex differences in vascular contributions to Alzheimer's disease.
Up to 80% of those with Alzheimer's disease have underlying vascular damage (VCID) and/or metabolic disease (prediabetes or diabetes). Alzheimer's disease is more prevalent in women than men.  The goal of this study is to determine sex differences in how metabolic disease and VCID alter Alzheimer's disease pathology and cognitive deficits using mouse models. This project was funded by Albany Medical College Start Up funds.


4) Role of Estrogen in Post-Menopausal Alzheimer’s Disease.
While it is know that Alzheimer's disease is more common in women than men, the reason for this sex difference is unknown.  Middle-aged women go through major hormonal changes during menopause that accelerate their development of risk factors for Alzheimer's disease. The goal of this study is to understand the important role of menopause and estrogen in Alzheimer's pathology.

5) Neuroimmune Changes with Aging and Dementia.
Neuroinflammation is known to increase with both aging and dementia.  In collaboration with Dr. Qi Yang's lab in the Immunology Department at Albany Medical College, we are assessing changes in a novel type of anti-inflammatory immune cell in the brain - group type 2 innate lymphoid cells (ILC2s). Activating these cells is showing promise in protecting against age-related decline in our mouse models. To hear more about this work, check out our recent interview in Newsweek.   

6) Investigating the Functional Impact of Alzheimer's Disease Risk Genes in Neuro-Vascular Interactions.
Vascular pathology is found in up to 80% of all Alzhiemer's disease cases.  In a multi-PI collaboration (with Dr. Sally Temple, Dr. Celeste Karch, Dr. Oscar Harari, Dr. Martin Kampmann, and Dr. Kevin Pumiglia), we are identifing key vascular risk genes for Alzheimer's disease and characterizing their impact on both vascular and cognitive function in several mouse models of Alzheimer's disease.  This work has been approved for funding by National Institue on Aging as a U01 consortium grant.  We will be hiring a new postdoc to work on this project soon!  Contact us if interested! 



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