Researchers here outline a new discovery regarding the origin of reduced blood flow in the aging brain; white blood cells are clogging up capillaries. It is well known that the supply of blood is reduced in tissues with age; this is studied in muscles and the brain, among other tissue types. Some researchers blame a reduction in capillary density in later life, others consider reduced capacity of the heart to pump blood uphill to the brain. A lesser flow of blood in any specific tissue will affect its function, especially in energy-hungry tissues such as the brain, as the supply of oxygen and nutrients is reduced.
In the case of the results reported here, I have to wonder whether this might tie in some way to the observed reduction in capillary density with age; does blockage by white blood cells result in significant capillary atrophy at the smallest scale of blood vessels? There are certainly other mechanisms by which that outcome could occur, and this may not be an important contribution even it does produce atrophy to some degree.
The existence of cerebral blood flow reduction in Alzheimer's patients has been known for decades, but the exact correlation to impaired cognitive function is less understood. "People probably adapt to the decreased blood flow, so that they don't feel dizzy all of the time, but there's clear evidence that it impacts cognitive function." A new study offers an explanation for this dramatic blood flow decrease: white blood cells stuck to the inside of capillaries, the smallest blood vessels in the brain. And while only a small percentage of capillaries experience this blockage, each stalled vessel leads to decreased blood flow in multiple downstream vessels, magnifying the impact on overall brain blood flow.
The work began with a study in which researchers were attempting to put clots into the vasculatures of Alzheimer's mouse brains to see their effect. "It turns out that the blockages we were trying to induce were already in there. It sort of turned the research around - this is a phenomenon that was already happening." The researchers determined that only about 2 percent of brain capillaries had "stalls" (blockages), but the cumulative effect of that small number of stalls was an approximately 20 percent overall decrease in brain blood flow, due to the slowing of downstream vessels by the capillaries that were stalled.
Recent studies suggest that brain blood flow deficits are one of the earliest detectable symptoms of dementia. To test the effect of the stalls on performance of memory tasks in Alzheimer's mice, they were given an antibody that interfered with the adhesion of white blood cells to capillary walls, which caused the stalled capillaries to start flowing again and thus increased overall brain blood flow. Memory function was improved within a few hours, even in aged mice with more advanced stages of Alzheimer's disease.