The Neurovascular Unit in Alzheimer’s Disease

Stephanie Taylor1, Gabor Petzold1


Alzheimer’s disease (AD) is the most common form of dementia affecting the aging population worldwide. Dysfunction of the brain’s vasculature has been linked with pathology of the disease, and indeed small brain bleeds (cerebral microbleeds, CMBs) seen on MRI or in autopsies are higher in patients with AD than in the general population. When brain vessels rupture, they release toxic substances that can potentially increase damage. Microglia and astrocytes survey the microenvironment for hints of damage, but they have been also identified as important neurotoxic effectors in different disease models.
Here, we aimed to explore, in animal models of AD or cerebral amyloid angiopathy (CAA), how the progression of amyloidosis effects these cells’ response to damage, and whether behavioural deficits and decreased vessel integrity (leakiness) and repair (survival) are observed.
In comparing healthy "wild-type" animals to those with AD or CAA; we found that vessels that do not regain flow and are lost have increased permeability of fluorescent dyes injected 30 minutes after the bleed, increased microglia accumulation around the damaged vessel at 24hrs post bleed and that mice with AD or CAA tended to lose more vessels. We also observed increased Ca2+ signalling in astrocytes in the area around the damaged vessel after induction of the bleed.