Scientists increasingly recognize Alzheimer’s as a disease process that begins years before symptoms of dementia become evident. Now, new research has found changes in the brain and body up to 20 years before Alzheimer’s symptoms arise.
The research, published in the journal Lancet Neurology, looked at a large extended South American family in Colombia that carried a gene for the early-onset form of Alzheimer’s, which typically arises before age 60. About 30 percent of the 5,000 family members carry the defective gene. Inheriting the gene, called presenelin 1, guarantees that you’ll get Alzheimer’s at a relative young age.
Among the relatives, members who had the gene typically began to develop serious memory problems in their mid-40s, with full-flown Alzheimer’s by their early 50s. The scientists discovered that many young people in the family, some as young as 18, had changes in their brain, blood and nervous system that presaged the onset of Alzheimer’s decades later.
The changes are the earliest signs yet detected of Alzheimer’s disease. Although it was a study of early-onset disease, scientists have noted related changes in those with the far more common late-onset form of Alzheimer’s.
Using brain scans and tests of the spinal fluid and blood, the researchers examined dozens of young people, ages 18 to 26, in the family. Only some carried the Alzheimer’s gene, and none had any memory problems or other symptoms.
In those that carried the gene, the scientists found various changes that appear to indicate the earliest signs of Alzheimer’s. Family members destined to develop the disease had greater activation in the hippocampus, a part of the brain critical for memory. It was as if this part of the brain had to work harder for day-to-day function, the researchers speculated.
Those who had the gene also had less gray matter in parts of the brain known to be affected by Alzheimer’s. They also had elevated levels of beta-amyloid, a toxic protein that builds up in the brains of those with Alzheimer’s, in the blood and spinal fluid.
Additional research by the team looked at family members ranging in age from 20 to 56. They found that brain plaques, a hallmark of Alzheimer’s, began to appear in the brains of family members who carried the gene by their late 20s, 15 years before memory problems became evident. Plaque is formed as beta-amyloid levels increase and clump together to form hard deposits in the brain. Plaque levels in the brain rose through affected family members’ late 20s and into their 30s, and then tended to level off around age 37.
"These findings suggest that brain changes begin many years before the clinical onset of Alzheimer's disease, and even before the onset of amyloid plaque deposition,” study author Dr. Eric Reiman of the Banner Alzheimer’s Institute in Phoenix, Arizona. “They raise new questions about the earliest brain changes involved in the predisposition to Alzheimer's and the extent to which they could be targeted by future prevention therapies."
Current Alzheimer’s drugs do little to stop the relentless downward progression of the disease. But scientists hope that earlier treatments, before damage to the brain becomes extensive, may be the most effective way to curb Alzheimer’s.
If scientists could reliably identify signs that someone is likely to get the disease, they could begin treatment earlier, possibly warding off the onset of Alzheimer’s symptoms years down the road. Someone who has no obvious memory problems, for example, might remain problem-free if they take a drug that targets beta-amyloid buildup.
The researchers are studying other family members, ages 7 to 17, to see whether brain changes occur at an even younger age.
Source: Eric Rieman, et al: “Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study.” Lancet Neurology, Dec. 1, 2012