More and more data suggest that treatment for Alzheimer’s disease may be more effective if started early, even before symptoms appear. In addition, recent clinical trials of treatments for mild to moderate Alzheimer’s have failed, suggesting that waiting to treat the disease until these stages may be too late, and that once the degenerative process has started it cannot be stopped. But since Alzheimer’s has no identifiable markers in its early stages, how would doctors know when and whom to treat?
Alzheimer’s is a form of dementia that causes an irreversible loss in brain function and gradually gets worse over time, affecting memory, thinking, and behavior. Buildup of insoluble proteins in the brain causes amyloid plaques or neurofibrillary tangles, two hallmarks of the disease, along with a loss in connections between electrically active nerve cells called neurons. There is no definite diagnosis other than autopsy.
A recent study of an extended family of 5,000 people from Colombia who inherited a form of Alzheimer’s revealed that the disease begins much earlier and the deterioration of the brain occurs in more ways than previously thought. Affected family members had mild problems thinking and remembering at an average age of 45 and dementia at 53. However, researchers also noticed changes in affected family members at younger ages, before the first signs of plaques in the brain.
The study compared twenty 18- to 26-year-old family members who carried a mutation called presenilin1 E280A and were very likely to develop early onset Alzheimer’s with 24 non-carriers. Both groups underwent a variety of tests including MRIs, memory tests, cognitive tests, blood tests and cerebral spinal fluid sampling. The groups did not differ significantly in their dementia ratings or psychological scores. However, carriers had fewer neurons in several regions of the brain that are affected by Alzheimer’s. Carriers also had higher levels of the amyloid protein that causes plaques in their cerebrospinal fluid.
Previous studies of Alzheimer’s patients showed they have lower levels of amyloid than normal, which had been attributed to amyloid accumulating in the brain. Based on this information, scientists thought Alzheimer’s was explained by the progressive buildup of amyloid in plaques that causes brain cells to die, leading to symptoms of Alzheimer’s. This new study suggests that there are early changes in the brain even before amyloid plaques appear.
This challenges what we know about when and how Alzheimer’s develops. Inherited, early-onset Alzheimer’s may be caused by the body producing too much amyloid, while late-onset Alzheimer’s may be the result of the body’s inability to clear amyloid from the brain.
Researchers are now focusing on family members ages 7 to 17 to determine if they can detect any brain differences even earlier.
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