A healthy brain translates into a healthy blood-brain barrier (BBB) which is a complex series of blood vessels in the brain. When the BBB malfunctions, it may lead to diabetes, multiple sclerosis, or Alzheimer’s disease.
A recent article in NeuroScience News reports that researchers at the University of Washington have reviewed over 150 studies about the effect aging has on the BBB. Their study has been published in the March 15th issue of Nature Aging.
Yet there is no definitive answer as to whether or not changes in the BBB actually alter various brain functions. The lead author of the current study acknowledges that it is often difficult to differentiate between early disease and normal aging.
Researchers have found that older, healthy individuals have a minor amount of leakage in their brain and the associated forgetfulness is thought to be “normal aging”. But now the question that arises is whether this “normal aging” is actually early Alzheimer’s disease.
About the Blood-Brain Barrier
Since the brain is sensitive to toxic substances found in the blood, the primary function of the BBB becomes one of preventing unregulated leakage of these substances from the blood to the brain. The BBB also pumps toxins out of the brain and conversely sends informational molecules and nutritional substances to the BBB.
About ApoE4 Allele
ApoE4 is a primary genetic risk in Alzheimer’s disease. Researchers have found that if a person carries ApoE4, there is an increase of BBB changes that are age-related.
There are three human gene variants that are carriers for brain lipids: Apo2, Apo3, and Apo4, yet only Apo4 increases the risk of Alzheimer’s.
A study from the Max Delbruck Center reports that ApoE4 disrupts the neuroprotective action of sortilin in neuronal lipid metabolism.
With respect to ApoE3, sortilin binds the lipid-loaded ApoE3, deposits its load into the neurons, and returns to the surface to begin anew. Repetition of this process supplies neurons with sufficient essential fatty acids. But not so with ApoE4.
When sortilin binds ApoE4 and is transported into the cell’s interior, it clumps up inside the cell and cannot return to the cell surface. Therefore there are fewer fatty acids generated, and the cell becomes inflamed and vulnerable. This causes cell death and an increased risk of Alzheimer’s disease.
Individuals who are healthy have a minor accumulation of plaque in their brains as they age. But people with ApoE4 have an even smaller reduction of amyloid beta-peptide in their brains and an increased buildup of plaque.
About Astrocytes and Pericytes
The study reported that two cells change in the BBB as we age: astrocytes and pericytes. New studies suggest that the leak in the BBB that appears in the brains of Alzheimer’s patients may possibly be caused by a loss of pericytes. Preserving the pericyte function or even transplantation may lead to a healthier BBB.
New Alzheimer’s Disease Target
Astrocytes are associated with excess activity.
In a newly announced study conducted at USC’s Keck School of Medicine, researchers noted that the search for an Alzheimer’s cure should begin much earlier than currently believed. The targets are the brain’s tiny blood vessels that begin to break down at age forty.
About half of all dementia begins with the breakdown of these blood vessels. Their malfunction allows toxic substances to invade the brain followed by a disruption in communication.
People with this disorder also have “small vessel disease” where the protective myelin sheath surrounding the brain breaks down. The process begins with damage to the pericytes which protect the tiny blood vessels in the brain.
Researchers at USC suggest that their pericyte studies may provide a basis for new Alzheimer’s treatments.
