Most scientists consider plaques and tangles in the brain to be the hallmarks of Alzheimer’s disease.  However, they are still trying to figure out how these plaques and tangles cause brain cells to die.  And we do not yet know why up to 30% of those with plaques and tangles do not develop symptoms of Alzheimer’s disease.

This week, the Harvard Medical School researchers released the results of a study, reported in Nature, which suggest possible answers to these questions, opening up new avenues of research.  The paper reports that another protein – REST – may protect against the development of Alzheimer’s disease and other neuro-degenerative diseases, such as Parkinson’s and Lewy Body dementia.

REST is a protein that has been known for its role in fetal development.  Until now, researchers assumed that REST had no role to play after the fetus matured.  Levels of REST after birth in normally developing brains are very low.

The Harvard study studied brain tissue obtained from brain banks maintained by Rush Medical Center, Massachusetts General Hospital, and Brigham and Women’s Hospital.   They examined tissue from those aged 20 to 35, and those between the ages of 73 and 106.  The tissue of the aged population came from individuals who agreed to cognitive testing, so the researchers were able to identify the cognitive functioning for each sample.

The examination revealed that levels of REST appear to increase as people age.  Those aged 20 to 35 had very low levels of REST, but most of the aged group had very high levels of REST, except for those with confirmed diagnoses of Alzheimer’s disease, frontotemporal or Lewy Bodies dementia.  The levels of REST found in this group were 3 times less than the levels of those with normal cognition.

There are other important findings in this paper:

• The researchers found that people with hallmark protein plaques and tangles who also had high levels of REST did not exhibit symptoms of dementia.
•  The lowered levels of REST among the cognitively impaired were not lower throughout the brain, but only in the pre-frontal cortex and hippocampus, areas that are known to be altered as Alzheimer’s disease progresses.
•  The researchers conducted follow up studies with mice and earthworms, which established an association between high levels of REST and the lack of dementia symptoms.

This study provides new avenues for researchers.  It may ultimately provide answers to why some people with abnormal build up of ABeta protein in their brains remain cognitively normal, and new drug therapies to protect against Alzheimer’s.