In a recently published article in the journal Neurology, investigators at the University of British Columbia have demonstrated that build-up of cerebral amyloid, a protein marker of Alzheimer disease, is more common in those with injury to the deep periventricular area of the brain.
The investigators used MRI scans to quantify the severity of damage to the small blood vessels of the brain by measuring periventricular white matter hyperintensities (PVWMH). The periventricular area is located deep within the brain, and therefore is very susceptible to reduced blood flow in the small blood vessels that originate at the surface of the brain.
In Alzheimer disease, blood flow can be reduced by build up of amyloid in the walls of small blood vessels, known as cerebral amyloid angiopathy (CAA). Therefore, increased PVWMH seen on MRI in patients with Alzheimer disease could represent increased CAA-related damage to the small blood vessels near the brain surface.
“Patients with moderate or severe damage to the cerebral small blood vessels have typically been excluded from participation in Alzheimer-related clinical trials including therapies targeting the build up of amyloid in the brain,” says Dr. Michael Marnane, lead author on the study and Heart and Stroke Foundation of Canada-funded postdoctoral fellow with the UBC Hospital Clinic for Alzheimer Disease and Related Disorders at the Djavad Mowafaghian Centre for Brain Health.
“Our findings suggest that these individuals are in fact even more likely to have significant amyloid build-up. At this stage it is unclear whether therapies that were unsuccessfully tested in those without significant cerebral vascular disease could be effective and safe in those with moderate or severe disease.”
This work was made possible by the participation of more than 1200 individuals in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). ADNI was conducted across over 50 sites in North America and led by Dr. Michael Weiner of UCSF, and locally at UBC by Dr. Howard Feldman and Dr. Robin Hsiung.
Dr. Marnane and his UBC-based team were able to use the ADNI data to develop a novel visual method for quantifying PVWMH that could be used to compare with cerebrospinal fluid and positron emission tomography measurements of brain amyloid build-up.
“Our next step is to see whether PVWMH is a predictor of Alzheimer pathology and CAA at autopsy,” says Dr. Marnane. “Better understanding the link between Alzheimer disease and damage to the small blood vessels in the brain could open the door to developing new therapies for a disease that so far has proven very difficult to treat.”
“It’s an exciting time as some of our colleagues at UBC, including Dr. Cheryl Wellington and Dr. Neil Cashman, have already begun to unlock the molecular mechanisms underlying the links between vascular disease, amyloid, and cognitive problems.”
Marnane M, Al-Jawadi OO, Mortazavi S, Pogorzelec KJ, Wang BW, Feldman HH, Hsiung GY; Alzheimer’s Disease Neuroimaging Initiative. Periventricular hyperintensities are associated with elevated cerebral amyloid. Neurology. 2016 Feb 9;86(6):535-43.