Alzheimer's Brain Discovery: Amyloid-beta Expression is Age-Dependent

It is known that age is a significant risk factor for many neurodegenerative diseases, including Alzheimer's disease; as the brain ages, the peptide amyloid-beta (Abeta) builds up in the brain, which has been connected to Alzheimer’s as well as dementia.

According to new research, the removal of Abeta from the brain is dependent on vitamin D, as well as a modification related to age in the manufacture of transporter proteins which transfer Abeta in and out of the brain.

Abeta accumulates in both the brains of Alzheimer’s patients as well as those without the disease, but as the brain ages, the expression of amyloid-beta transporters decreases, causes Abeta buildup in the brain.

The study was performed by researchers from Rhode Island Hospital and The Warren Alpert Medical School of Brown University.

Gerald Silverberg, a professor from the medical school, said that “while increased production of transporter proteins at the blood CSF barrier may help amyloid β [Abeta] removal from the older brain, production of these proteins eventually fails. This failure may be an important event in brain function as we age and for people with Alzheimer's disease."

Focusing on the transportation of Abeta from the blood to CSF and vice versa, the researchers discovered that LRP-1 and P-gp at the blood CSF barrier increased with age, which led to increasing removal of Abeta from the CSF and brain.

In conclusion, age-related changes in the choroid plexus (CP) Abeta transporters are connected to “a decrease in Abeta42 accumulation in the CP, and are reciprocal to the changes seen in these transporters at the [blood brain barrier] (BBB), suggesting a possible compensatory role for the BCSFB in Abeta clearance in aging,” the authors wrote.

An editor of the journal in which the study was published, Professor Tetsuya Terasaki from Tohoku University, Japan, was involved in a separate study investigating the role of vitamin D in the brain. The researchers of Tohoku University study the brains of mice and discovered that vitamin D injections improved the removal of Abeta.

Terasaki stated that “vitamin D appears increase transport of amyloid β [Abeta] across the blood brain barrier by regulating protein expression, via the vitamin D receptor, and also by regulating cell signaling via the MEK pathway.”

Lower levels of vitamin D are believed to be connected to decline in memory and cognition associated with aging.

“These results lead the way towards new therapeutic targets in the search for prevention of Alzheimer's disease," concluded Terasaki.

This research is published inBioMed Central's open access journal Fluids and Barriers of the CNS, where the full study is available on PDF.