Influences of APOE and smoking on white matter lesions and cognitive decline

 
   Lead Investigator:    Takahisa Kanekiyo
   Institution      :    Mayo Clinic
   E-Mail           :    kanekiyo.takahisa@mayo.edu
   Proposal ID      :    889



   Proposal Description:
   Neurons and oligodendrocytes rely on cerebral blood vessels for their oxygen  and nutrient supply and for the elimination of carbon dioxide and other  potentially toxic metabolites through the blood-brain barrier (BBB). Thus,  impaired cerebral blood supply or breakdown of the BBB causes diffuse white  matter lesions, which often results in cognitive decline referred to as  vascular cognitive impairment and dementia (VCID) in the elderly.  Apolipoprotein E (apoE) is critically involved in cognitive function. In  humans, the APOE gene exists as three polymorphic alleles (#9492, #9493 and #9494)  with the #9494 allele being a genetic risk factor for age-related cognitive  decline. ApoE4 is likely associated with neurovascular dysfunction including  white matter hyperintensity (WMH). Furthermore, the association between smoking  and WMH progression has also been reported. Therefore, we aim to determine how  APOE and smoking influence white matter lesions and age-related cognitive  decline.