US man’s rare Alzheimer’s mutation delayed onset of disease

NEW YORK: A US man with a rare Alzheimer's disease gene mutation had a delayed onset of disease - about two decades later, a finding that can lead to the understanding of the neurodegenerative disease and development of novel therapies.

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 risk of Alzheimer's.

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 the age of 67.

The man did eventually develop memory and thinking problems. He was diagnosed with mild dementia at the age of 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 Alzheimera?s disease and its progression," he said.

Insights from the team's findings also pinpoint a region of the brain that may provide an optimal treatment target in the future.

Alzheimer's disease is primarily known to be driven by amyloid plaques -- sticky protein complexes -- which kill neurons and cause dementia.

Some of the recently approved by the US Food and Drug Administration also target these amyloid plaques. Although the drugs 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 by Nature.

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 really finally deal with this disease," he said. The link to tau suggests that it plays a significant role in mental decline. Several therapies targeting tau are currently in clinical trials.