CHICAGO, May 6 (Reuters) - People who carry two copies

of the APOE4 gene are virtually guaranteed to develop

Alzheimer's and face symptoms at an earlier age, researchers

reported on Monday in a study that could redefine such carriers

as having a new genetic form of the mind-wasting disease.

The reclassification could change Alzheimer's research,

diagnosis and approaches to treatment, according to the

researchers, whose study was published in the journal Nature

Medicine.

"Through these data we are saying that perhaps this is a

genetic form of this disease, not merely a risk factor

indication," study co-author Sterling Johnson of the University

of Wisconsin's Alzheimer's Disease Research Center told

reporters in a briefing on the study.

Scientists have known for three decades that people with two

copies of APOE4 gene variant have significantly higher risk of

developing the disease than people with the most common version

of the APOE gene, known as APOE3. About 2% to 3% of the general

population, or about 15% of people with Alzheimer's, have two

copies of the APOE4 variant.

"This study adds compelling data to suggest that people with

two copies of this gene are almost guaranteed to develop

Alzheimer's if they live long enough, and that they will develop

Alzheimer's earlier than people without this gene," said

professor Tara Spires-Jones, an Alzheimer's researcher at the

University of Edinburgh who was not involved in the study.

Dr. Juan Fortea of the University of Barcelona and

colleagues studied more than 3,000 donated brains from the U.S.

National Alzheimer's Coordinating Center, as well as biological

and clinical data on more than 10,000 individuals from five

datasets in three countries.

They found that by the age of 65, at least 95% of people

with two copies of APOE4 - known as homozygotes - had abnormal

levels of an Alzheimer's-related protein called beta amyloid in

their spinal fluid, and 75% had positive brain scans for

amyloid.

Nearly all APOE4 homozygotes in the study had higher levels

of amyloid at age 65 than people who did not carry the risk

variant.

The findings suggest APOE4 homozygotes meet the three main

criteria for being a genetic disease: nearly everyone with these

two gene variants have Alzheimer's biology; they develop

symptoms at about the same rate; and clinical and biological

changes occur in a predictable sequence, the researchers said.

Professor David Curtis of the UCL Genetics Institute, who

was not involved in the research, remained unconvinced. "I do

not see anything in this paper to justify the claim that

carrying two copies of APOE4 represents some 'distinct genetic

form' of Alzheimer's disease'," he said in a statement.

"No matter how many (copies) of APOE4 one carries the

underlying disease processes seem similar across cases of

Alzheimer's disease," he said.

The findings could have implications for the recently

approved Alzheimer's treatment Leqembi from Eisai ( ESALF ) and

Biogen, a drug that removes amyloid from the brain.

In clinical trials, patients with two copies of the APOE4

variant have much higher rates of brain bleeding and swelling

associated with the treatment. Because of this, some centers do

not treat these patients, Dr. Reisa Sperling, an Alzheimer's

researcher at Mass General Brigham who worked on the study, said

in a briefing with reporters.

"This research really suggests that we should be treating

them quite early at a younger age and at an early stage of

pathology because we know they're very, very likely to progress

to impairment quickly," she said.

Spires-Jones said the work highlights the need for more

research on how genes affect Alzheimer's disease as people age.

Other genetic forms of Alzheimer's include Autosomal-dominant

Alzheimer's Disease, which is caused by mutations in two

different genes, and Down syndrome.

Most of the study population involved people of European

ancestry, and the team noted that more work needs to be done in

people of African descent, a population in which APOE4 appears

to convey a lower risk of Alzheimer's disease.