(AP) - Sen. Edward M. Kennedy of Massachusetts, the lastsurviving brother in a political dynasty and one of the mostinfluential senators in history, died Tuesday night at his home onCape Cod after a year-long struggle with brain cancer. He was 77. In nearly 50 years in the Senate, Kennedy served alongside 10presidents - his brother John Fitzgerald Kennedy among them -compiling an impressive list of legislative achievements on healthcare, civil rights, education, immigration and more. His only run for the White House ended in defeat in 1980. Morethan a quarter-century later, he handed then-Sen. Barack Obama anendorsement at a critical point in the campaign for the Democraticpresidential nomination, explicitly likening the young contender toPresident Kennedy. To the American public, Kennedy was best known as the lastsurviving son of America's most glamorous political family, fatherfigure and, memorably, eulogist of an Irish-American clan plaguedagain and again by tragedy. Kennedy's death triggered an outpouring of superlatives, fromDemocrats and Republicans as well as foreign leaders. "An important chapter in our history has come to an end. Ourcountry has lost a great leader, who picked up the torch of hisfallen brothers and became the greatest United States senator ofour time," Obama said in a written statement. "For five decades, virtually every major piece of legislationto advance the civil rights, health and economic well being of theAmerican people bore his name and resulted from his efforts," saidObama, vacationing at Martha's Vineyard off the Massachusettscoast. Kennedy's family announced his death in a brief statementreleased early Wednesday. "We've lost the irreplaceable center of our family and joyouslight in our lives, but the inspiration of his faith, optimism, andperseverance will live on in our hearts forever," the statementsaid. "We thank everyone who gave him care and support over thislast year, and everyone who stood with him for so many years in histireless march for progress toward justice, fairness andopportunity for all." Senate Majority Leader Harry Reid of Nevada issued a statementthat said, "It was the thrill of my lifetime to work with TedKennedy.....The liberal lion's mighty roar may now fall silent, buthis dream shall never die." Former First Lady Nancy Reagan said that her husband and Kennedy"could always find common ground, and they had great respect forone another." Kennedy was elected to the Senate in 1962, taking the seat thathis brother John had occupied before winning the White House, andserved longer than all but two senators in history. His own hopes of reaching the White House were damaged - perhapsdoomed - in 1969 by the scandal that came to be known asChappaquiddick, an auto accident that left a young woman dead. Hesought the White House more than a decade later, lost theDemocratic nomination to President Jimmy Carter, and bowed out witha stirring valedictory that echoed across the decades: "For allthose whose cares have been our concern, the work goes on, thecause endures, the hope still lives and the dream shall neverdie." Kennedy was diagnosed with a cancerous brain tumor in May 2008and underwent surgery and a grueling regimen of radiation andchemotherapy. He made a surprise return to the Capitol last summer to cast thedecisive vote for the Democrats on Medicare. He made sure he wasthere again last January to see his former Senate colleague BarackObama sworn in as the nation's first black president, but suffereda seizure at a celebratory luncheon afterward. He also made a surprise and forceful appearance at last summer'sDemocratic National Convention, where he spoke of his own illnessand said health care was the cause of his life. His death occurredprecisely one year later, almost to the hour. He was away from the Senate for much of this year, leavingRepublicans and Democrats to speculate about the impact what hisabsence meant for the fate of Obama's health care proposals. Under state law, Kennedy's successor will be chosen by specialelection. In his last known public act, the senator urged stateofficials to give Democratic Gov. Deval Patrick the power to namean interim replacement. But that appears unlikely, leavingDemocrats in Washington with one less vote for the next severalmonths as they struggle to pass Obama's health care legislation. His death came less than two weeks after that of his sisterEunice Kennedy Shriver on Aug. 11. Kennedy was not present for thefuneral, an indication of the precariousness of his own health. In a recent interview with The Associated Press, Kennedy's sonRep. Patrick Kennedy, D-R.I., said his father had defied thepredictions of doctors by surviving more than a year with his fightagainst brain cancer. The younger Kennedy said that gave family members a surpriseblessing, as they were able to spend more time with the senator andto tell him how much he had meant to their lives. "There are very few people who have touched the life of thisnation in the same breadth and the same order of magnitude," Obamasaid in April as he signed the Edward M. Kennedy Serve America Actinto law. Kennedy arrived at his place in the Senate after a string offamily tragedies. He was the only one of the four Kennedy brothersto die of natural causes. Kennedy's eldest brother, Joseph, was killed in a plane crash inWorld War II. President John F. Kennedy was assassinated in Dallasin 1963. Sen. Robert F. Kennedy was gunned down in Los Angeles ashe campaigned for the 1968 Democratic presidential nomination. Years later, in 1999, John F. Kennedy Jr. was killed in a planecrash at age 38 along with his wife. It fell to Ted Kennedy to deliver the eulogies, to comfort hisbrothers' widows, to mentor fatherless nieces and nephews. It wasTed Kennedy who walked JFK's daughter, Caroline, down the aisle ather wedding. Tragedy had a way of bringing out his eloquence. Kennedy sketched a dream of a better future as he laid to resthis brother Robert in 1968: "My brother need not be idealized, orenlarged in death beyond what he was in life; to be rememberedsimply as a good and decent man, who saw wrong and tried to rightit, saw suffering and tried to heal it, saw war and tried to stopit." After John Jr.'s death, the senator said: "We dared to think,in that other Irish phrase, that this John Kennedy would live tocomb gray hair, with his beloved Carolyn by his side. But like hisfather, he had every gift but length of years." His own legacy was blighted on the night of July 18, 1969, whenKennedy drove his car off a bridge and into a pond onChappaquiddick Island, on Martha's Vineyard. Mary Jo Kopechne, a28-year-old worker with RFK's campaign, was found dead in thesubmerged car's back seat 10 hours later. Kennedy, then 37, pleaded guilty to leaving the scene of anaccident and received a two-month suspended sentence and a year'sprobation. A judge eventually determined there was "probable causeto believe that Kennedy operated his motor vehicle negligently ...and that such operation appears to have contributed to the death ofMary Jo Kopechne." At the height of the scandal, Kennedy went on nationaltelevision to explain himself in an extraordinary 13-minute addressin which he denied driving drunk and rejected rumors of "immoralconduct" with Ms. Kopechne. He said he was haunted by"irrational" thoughts immediately after the accident, andwondered "whether some awful curse did actually hang over all theKennedys." He said his failure to report the accident right awaywas "indefensible." After Chappaquiddick especially, Kennedy gained a reputation asa heavy drinker and a womanizer, a tragically flawed figure hauntedby the fear that he did not quite measure up to his brothers. Ashis weight ballooned, he was lampooned by comics and cartoonists inthe 1980s and '90s as the very embodiment of government waste,bloat and decadence. But in his later years, after he had remarried, he came to beregarded as a statesman on Capitol Hill, seen as one of the mosteffective, hardworking lawmakers Washington has ever seen. A barrel-chested figure with a swath of white hair, a boomingvoice and a thick, widely imitated Boston accent, he coupledfist-pumping floor speeches with his well-honed Irish charm andformidable negotiating skills. He was both a passionate liberal anda clear-eyed pragmatist, willing to reach across the aisle to getthings done. Kennedy's speech in accepting defeat to Carter electrified theDemocratic convention and turned out to be a defining moment. At48, he seemed liberated from the towering expectations and highhopes invested in him after the death of his brothers, and heplunged into his work in the Senate. First elected to the Senate in 1962 to his brother John's seat,easily re-elected in 2006, Kennedy served close to 47 years, longerthan all but two senators in history: Robert Byrd of West Virginia(50 years and counting) and the late Strom Thurmond of SouthCarolina, who died after a tenure of nearly 47½ years. Kennedy'scareer spanned 10 presidencies. His legislative achievements included bills to provide healthinsurance for children of the working poor, the landmark 1990Americans with Disabilities Act, Meals on Wheels for the elderly,abortion clinic access, family leave, and the Occupational Safetyand Health Administration. He was also a key negotiator on legislation creating a Medicareprescription drug benefit for senior citizens and was a drivingforce for peace in Ireland and a persistent critic of the war inIraq. Kennedy did not always prevail. In late 2008, he unsuccessfullylobbied for niece Caroline's appointment to the Senate from NewYork. New York Gov. David Paterson chose then-Rep. KirstenGillibrand instead. Wildly popular among Democrats, Kennedy routinely wonre-election by large margins. He grew comfortable in his role asRepublican foil and leader of his party's liberal wing. President George W. Bush welcomed Kennedy to the Rose Garden onseveral occasions as he signed bills that the Democrat helpedwrite. "He's the kind of person who will state his case, sometimesquite eloquently and vociferously, and then on another issue willcome along and you can work with him," Bush said shortly beforehis first term began in 2001. But Bush was also the target of some of Kennedy's sharpestattacks. Kennedy assailed the Iraq war as Bush's Vietnam, aconflict "made up in Texas" and marketed by the Bushadministration for political gain. Kennedy and his niece Caroline shook up the Democraticestablishment in January 2008 when they endorsed Obama over HillaryRodham Clinton for the nomination for president. After Obama won in November, Kennedy renewed words once spokenby his brother John, declaring: "The world is changing. The oldways will not do. ... It is time for a new generation ofleadership." Born in 1932, the youngest of Joseph and Rose Kennedy's ninechildren, Edward Moore Kennedy was part of a family bristling withpolitical ambition, beginning with maternal grandfather John F."Honey Fitz" Fitzgerald, a congressman and mayor of Boston. Round-cheeked Teddy was thrown out of Harvard in 1951 forcheating, after arranging for a classmate to take a freshmanSpanish exam for him. He eventually returned, earning his degree in1956. He went on to the University of Virginia Law School, and in1962, while his brother John was president, announced plans to runfor the Senate seat JFK had vacated in 1960. A family friend hadheld the seat in the interim because Kennedy was not yet 30, theminimum age for a senator. Kennedy was immediately involved in a bruising primary campaignagainst state Attorney General Edward J. McCormack, a nephew ofU.S. House Speaker John W. McCormack. "If your name was simply Edward Moore, your candidacy would bea joke," chided McCormack. Kennedy won the primary by 300,000 votes and went on tooverwhelmingly defeat Republican George Cabot Lodge, son of thelate Ambassador Henry Cabot Lodge, in the general election. Devastated by his brothers' assassinations and injured in a 1964plane crash that left him with back pain that would plague him fordecades, Kennedy temporarily withdrew from public life in 1968. Buthe re-emerged in 1969 to be elected majority whip of the Senate. Then came Chappaquiddick. Kennedy still handily won re-election in 1970, but he lost hisleadership job. He remained outspoken in his opposition to theVietnam War and support of social programs but ruled out a 1976presidential bid. In the summer of 1978, a Gallup Poll showed that Democratspreferred Kennedy over President Carter 54 percent to 32 percent. Ayear later, Kennedy decided to run for the White House with acampaign that accused Carter of turning his back on the Democraticagenda. The difficult task of dislodging a sitting president wascompounded by Kennedy's fumbling answer to a question posed by CBS'Roger Mudd: Why do you want to be president? "Well, it's um, you know you have to come to grips with thedifferent issues that, ah, we're facing," Kennedy said. "I mean,we can, we have to deal with each of the various questions of theeconomy, whether it's in the area of energy ..." He bowed out of the race after getting roundly beaten by Carterin the primaries and losing a rules battle at the Democraticconvention. Later, when asked to assess the campaign, he replied:"Well, I learned to lose, and for a Kennedy that's hard." Kennedy married Virginia Joan Bennett, known as Joan, in 1958.They divorced in 1982. In 1992, he married Washington lawyerVictoria Reggie. His survivors include a daughter, Kara KennedyAllen; two sons, Edward Jr. and Patrick, a congressman from RhodeIsland; and two stepchildren, Caroline and Curran Raclin. In 1991, Kennedy roused his nephew William Kennedy Smith and hisson Patrick from bed to go out for drinks while staying at thefamily's Palm Beach, Fla., estate. Later that night, a woman Smithmet at a bar accused him of raping her at the home. Smith was acquitted, but the senator's carousing - and testimonyabout him wandering about the house in his shirttails and no pants- further damaged his reputation. Kennedy offered a mea culpa in a speech at Harvard that October,recognizing "my own shortcomings, the faults in the conduct of myprivate life." Later on, his second wife appeared to have a calming influenceon him, helping him rehabilitate his image. Kennedy's family life has been marked by illness. Edward Jr. lost a leg to bone cancer in 1973 at age 12. Kara hada cancerous tumor removed from her lung in 2003. In 1988, Patrickhad a noncancerous tumor pressing on his spine removed. He has alsostruggled with depression and addiction and announced in June thathe was re-entering rehab. Kennedy's memoir, "True Compass," is set to be published inthe fall.