RAFAH, Gaza Strip/CAIRO/JERUSALEM — Palestinian militant group Hamas on Monday agreed to a Gaza ceasefire proposal from mediators, but Israel said the terms did not meet its demands and pressed ahead with strikes in Rafah while planning to continue negotiations on a deal.

The developments in the seven-month-old war came as Israeli forces struck Rafah on Gaza’s southern edge from the air and ground and ordered residents to leave parts of the city, which has been a refuge for more than a million displaced Palestinians.

Hamas said in a brief statement that its chief, Ismail Haniyeh, had informed Qatari and Egyptian mediators that the group accepted their proposal for a ceasefire.

Israeli Prime Minister Benjamin Netanyahu’s office said later that the truce proposal fell short of Israel’s demands but Israel would send a delegation to meet with negotiators to try to reach an agreement.

Qatar’s foreign ministry said its delegation will head to Cairo on Tuesday to resume indirect negotiations between Israel and Hamas.

In a statement, Mr. Netanyahu’s office added that his war cabinet approved continuing an operation in Rafah. Jordan’s Foreign Minister Ayman Safadi said on social media site X that Mr. Netanyahu was jeopardizing a ceasefire by bombing Rafah.

An Israeli official, speaking on condition of anonymity, said the proposal that Hamas approved was a watered-down version of an Egyptian offer and included elements that Israel could not accept.

“This would appear to be a ruse intended to make Israel look like the side refusing a deal,” said the Israeli official.

Another official briefed on the agreement said Hamas had agreed to the phased ceasefire and hostage release deal Israel proposed on April 27 with only minor changes that did not affect the main parts of the proposal.

US State Department spokesman Matthew Miller said Washington would discuss the Hamas response with its allies in the coming hours, and a deal was “absolutely achievable.” More than 34,600 Palestinians have been killed in the conflict, according to Gaza health officials. The United Nations (UN) has said famine is imminent in the enclave.

The war began when Hamas militants attacked Israel on Oct. 7, killing about 1,200 people and abducting 252 others, of whom 133 are believed to remain in captivity in Gaza, according to Israeli tallies.

RAFAH HIT BY STRIKES
Any truce would be the first pause in fighting since a week-long ceasefire in November, during which Hamas freed around half of the hostages.

Since then, all efforts to reach a new truce have foundered over Hamas’ refusal to free more hostages without a promise of a permanent end to the conflict, and Israel’s insistence that it would discuss only a temporary pause.

Taher Al-Nono, a Hamas official and adviser to Haniyeh, told Reuters the proposal met the group’s demands for reconstruction efforts in Gaza, return of displaced Palestinians and a swap of Israeli hostages for Palestinian prisoners in Israeli jails.

The Hamas deputy chief in Gaza, Khalil Al-Hayya, told Al Jazeera television the proposal comprised three phases of six weeks each, with Israel to pull its troops out of Gaza in the second phase.

Earlier on Monday, Israel ordered the evacuation of parts of Rafah, the city on the Egyptian border that has served as the last sanctuary for around half of Gaza’s 2.3 million residents.

An Israeli strike on a house in Rafah killed five Palestinians, including a woman and a girl, medics said.

Israel believes that a significant number of Hamas fighters, along with potentially dozens of hostages, are in Rafah and has said that victory requires taking the key city.

Israel’s closest ally, the United States, has called on it not to assault Rafah, saying it must not do so without a full plan in place to protect civilians there, which has yet to be presented.

A separate US official said that Washington is concerned about Israel’s latest strikes against Rafah but does not believe they represent a major military operation.

Israel said on Monday it was conducting limited operations on the eastern part of Rafah. Palestinian residents said there were massive air strikes.

“They have been firing since last night and today after the evacuation orders, the bombardment became more intense because they want to frighten us to leave,” Jaber Abu Nazly, a 40-year-old father of two, told Reuters via a chat app.

“Others are wondering whether there is any place safe in the whole of Gaza,” he added.

Instructed by Arabic text messages, phone calls and flyers to move to what the Israeli military called an “expanded humanitarian zone” around 20 km (12 miles) away, some Palestinian families began trundling away in chilly spring rain.

Some piled children and possessions onto donkey carts, while others left by pick-up or on foot through muddy streets.

As families dismantled tents and folded belongings, Abdullah Al-Najar said this was the fourth time he had been displaced since the fighting began seven months ago.

“God knows where we will go now. We have not decided yet.” — Reuters

CHICAGO — 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.

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 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 US National Alzheimer’s Coordinating Center, as well as biological and clinical data on more than 10,000 individuals from three countries.

They found that by age 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 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.

TREATMENT IMPLICATIONS
The findings could have implications for the recently approved Alzheimer’s treatment Leqembi from Eisai 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.

The findings suggest they should be treated at a younger age because “we know they’re very, very likely to progress to impairment quickly,” she said.

Dr. Samuel Gandy, an Alzheimer’s researcher at Mount Sinai in New York, said the findings stress the need to enroll APOE4 homozygotes into trials designed to prevent the disease before they develop symptoms. Sperling is conducting one such trial.

Heather Snyder of the Alzheimer’s Association said the findings, if correct, could have significant implications for how disease risk is assessed, how it is studied in clinical trials and how treatments are developed.

The new designation would be for Alzheimer’s that develops later in life. Other genetic forms include Autosomal-dominant Alzheimer’s Disease, which is caused by mutations in three different genes, and Down syndrome.

A key limitation of the study is that it involved mostly people of European ancestry. The team said more study is needed in people of African descent, a population in which APOE4 appears to convey a lower risk of Alzheimer’s disease. — Reuters