A rare genetic mutation in an American man delays the onset of Alzheimer’s disease by two decades

Representative Image (IANS)

Representative picture


An American man who carried a rare genetic mutation for Alzheimer’s disease had a delayed onset of the disease – about two decades later.

This is the second such case in the world. But the man belongs to the same family, of which 6,000 members carry the presenilin-1 gene, or PSEN1, commonly known to increase the risk of Alzheimer’s.

This discovery may improve understanding of the disease and help develop new therapies.

The study, published in the journal natural medicine, revealed that based on family history, the man was believed to develop memory loss and other symptoms of Alzheimer’s disease in his 40s or 50s. However, due to a mutation in the PSEN1 gene, he maintained full cognitive function until age 67.

The man eventually developed memory and thinking problems. He was diagnosed with mild dementia at 72, then experienced memory decline and an infection. He died of pneumonia at age 74.

The first of these cases was a female relative who remained cognitively intact into her 70s.

“The genetic variant we have identified points to a pathway that may produce extreme resilience and protection against Alzheimer’s disease symptoms,” said co-lead author Joseph Arboleda-Velasquez, associate professor of ophthalmology at Massachusetts. Eye and Ear, Harvard Medical School.

“These are the kinds of insights we can’t get without patients. They show us what’s important when it comes to protection and challenge many of the field’s assumptions about Alzheimer’s disease and its progression,” said he declared.

Information from the team’s findings also identifies a region of the brain that could provide an optimal treatment target.

Alzheimer’s disease is primarily known to be caused by amyloid plaques – sticky protein complexes – which kill neurons and cause dementia.

Some drugs recently approved by the United States Food and Drug Administration also target these amyloid plaques. Although the drugs effectively remove amyloid from the brain, it only leads to moderate improvement in rates of cognitive decline.

The study, however, challenged the theory citing high levels of amyloid plaques in the human brain.

“The fact that the man remained mentally healthy for so long despite having numerous amyloid plaques in his brain suggests that Alzheimer’s disease is more complicated,” said Yadong Huang, a neurologist at the Gladstone Institutes in San Francisco, in California.

He suggests that there could be several subtypes of Alzheimer’s disease, only some of which are caused by amyloid.

“We need different pathways to deal with this disease finally,” he said. The link to tau suggests that it plays an important role in mental decline. Several tau-targeting therapies are currently in clinical trials.


The above article was published from a telegraphic source with minimal changes to the title and text.

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