A US man with a rare Alzheimer’s gene mutation had a delayed disease onset — about two decades later.
This is the world’s second such case. But the man belongs to the same family, of which 6,000 family members carry the gene presenilin-1, or PSEN1 — commonly known to raise Alzheimer’s risk.
This finding can improve understanding of the disease and aid in developing novel therapies.
The study, published in the journal Nature Medicine, revealed that based on family history, the man was supposed to develop memory loss and other symptoms of Alzheimer’s in his 40s or 50s. However, because of a mutation in the gene PSEN1, he maintained full cognitive function until age 67.
The man did eventually develop memory and thinking problems. He was diagnosed with mild dementia at 72, then experienced more memory decline and an infection. He died of pneumonia at age 74.
The first such case was a woman from the same family who remained cognitively unimpaired until her 70s.
“The genetic variant we have identified points to a pathway that can produce extreme resilience and protection against Alzheimer’s disease symptoms,” said co-senior author Joseph Arboleda-Velasquez, associate professor of ophthalmology at Massachusetts Eye and Ear, Harvard Medical School.
“These are the kinds of insights we cannot gain without patients. They are showing us what’s important when it comes to protection and challenging many of the field’s assumptions about Alzheimer’s disease and its progression,” he said.
Insights from the team’s findings also pinpoint a brain region that may provide an optimal treatment target.
Alzheimer’s disease is primarily known to be driven by amyloid plaques — sticky protein complexes — which kill neurons and cause dementia.
Some drugs recently approved by the US Food and Drug Administration also target these amyloid plaques. Although the medicines effectively remove amyloid from the brain, it leads to only a moderate improvement in rates of cognitive decline.
The study, however, challenged the theory citing high levels of amyloid plaques in the man’s brain.
“The fact that the man stayed mentally healthy for so long despite the many amyloid plaques in his brain suggests that Alzheimer’s is more complicated,” Yadong Huang, a neurologist at the Gladstone Institutes in San Francisco, California, was quoted as saying.
He suggests that there could be multiple subtypes of Alzheimer’s, only some of which are driven by amyloid.
“We do need different pathways to deal with this disease finally,” he said. The link to tau suggests it plays a significant role in mental decline. Several therapies targeting tau are currently in clinical trials.
The above article has been published from a wire source with minimal modifications to the headline and text.