Those who study Alzheimer's disease are divided into two camps: the ßaptists, who see ß-amyloid plaques as the main cause of the disease, and the tauists, who believe that tau fibrils are to blame. A connection between the two comes with the discovery that glycosaminoglycans, which are known to be associated with plaques, are necessary for the assembly of tau into fibrils.
LONDON (Oct 9, 1996 9:48 p.m. EDT) - British scientists have found new clues about one of the classic pathological features of Alzheimer's disease that could eventually lead to an effective treatment for the degenerative brain illness.
In a report in the scientific journal Nature on Wednesday, Michel Goedert and colleagues at the MRC Laboratory of Molecular Biology in Cambridge, England, described how they reproduced abnormal filaments which make up neurofibrillary "tangles" - one of the two defining characteristics of Alzheimer's disease.
"It is the first time this has been done," Goedert told Reuters in a telephone interview. To make the filaments, Goedert mixed a protein called "tau" with substances known as glycosaminoglycans, which are sugars. The filaments make up the neurofibrillary tangles.
"The number of tangles (in the brain tissues of Alzheimer patients) correlates quite well with degrees of impairment. The more angles, the greater the impairment," he added. Goedert said the finding could present a way in which drugs to combat the tangles may be tested in laboratory conditions.
"Interactions between sulphated glycosaminoglycans and tau may thus be the central event in the development of nerufibrillary pathology in Alzheimer's disease," Goedert wrote in Nature.
Alzheimer's disease, which characterised by dementia and disorientation, afflicts nearly 10 percent of people over the age of 65 worldwide. Former U.S. president Ronald Reagan is a sufferer, as was the late American actress Rita Hayworth. The disease robs people of their memories and their ability to think, learn and take care of themselves.
A defining characteristic of the neuropathology of Alzheimer's disease is the presence
of neurofibrillary deposits. These are largely made up of paired helical filaments
(PHFs), composed of the microtubule-associated protein tau in a hyperphosphorylated
state. But what triggers their formation? Goedert et al. show that under
physiological conditions in vitro, sulphated glycosaminoglycans such as
heparin induce tau (whether phosphorylated or not) to form PHFs. Moreover, heparin
prevents tau from binding to microtubules, promoting microtubule disassembly, and
heparan sulphate is found together with tau in affected regions of the brain from the
earliest stages of Alzheimer's disease. Sulphated glycosaminoglycans may therefore
play a key role in the pathology of the condition.
M Goedert, R Jakes, M G Spillantini, M Hasegawa, M J Smith & R A Crowther
Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans
WASHINGTON - Mental impairment is not a "normal" part of aging and many cases of dementia can be treated, according to U.S. health guidelines released Wednesday. Even when the problem cannot be cured, such as Alzheimer's disease, early diagnosis is still advisable. "Early recognition of Alzheimer's disease or identification of other types of dementias can prevent costly and inappropriate treatment and give patients and family members time to address the complex financial, legal and medical conditions these conditions present," said Paul Costa of the National Institute on Aging, and the co-chair of the panel that drew up the guidelines.
The clinical practice guidelines are the last in a series drawn up by the Agency for Health Care Policy and Research, part of the U.S. Department of Health and Human Services. About one in five apparent cases of dementia are treatable, due to such disorders as depression or drug interaction, which is a particular problem among older people taking several medications for chronic conditions.
Yet many people, including some health care professionals, regard such symptoms as a difficulty absorbing new information, problems in handling complex tasks or trouble with spatial orientation as sad but normal parts of aging.
But according to the guidelines, they are instead signals that a doctor should be consulted. If Alzheimer's is suspected, the elderly person should be followed carefully.
Forgetfulness is not a part of growing old -- and doctors, family members and patients should regard it as medically important, according to new federal guidelines for treating Alzheimer's disease. The guidelines, issued by the Agency for Health Care Policy and Research, said the memory-destroying fatal disorder often goes undiagnosed in early stages by primary care doctors.
"Many health care professionals, as well as patients, their families and friends, mistakenly view the early symptoms of Alzheimer's disease as inevitable consequences of aging," said Health and Human Services secretary Donna R. Shalala. In modern managed care medical practices, many patients need the approval of primary care doctors to seek the treatment of specialists, said Cheryl Williams, vice president of medical and scientific affairs of the Alzheimer's Association. Many primary care doctors simply don't recognize the early of symptoms of the memory-destroying disease.
Williams said about 25 percent of Alzheimer's patients could be diagnosed earlier if primary care physicians were alerted to look for the disease and to eliminate other causes of memory loss. "Early recognition of Alzheimer's disease, or identification of other types of dementias, can prevent costly and inappropriate treatment, and give patients and family members time to address complex financial, legal and medical issues these conditions present," said Paul T. Costa Jr. of the National Institute of Aging and a co-author of the guidelines.
About 20 percent of dementias in the elderly are caused by conditions that can be treated and improved. Experts said the new guidelines will help doctors recognize and treat these conditions. Williams said a final, positive verification of Alzheimer's can be made only at autopsy, but that specialists now are quick to detect evidence of the disorder. Primary care doctors, however, must recognize patients who have dementia in order for patients to be referred to specialist, she said.
CHICAGO (Sep 25, 1996 01:42 a.m. EDT) -- Alzheimer's disease among men of Japanese ancestry is twice as common in Hawaii as it is in Japan, boosting the theory that environmental factors play a role in the development of the mind-robbing illness, researchers say.
Exactly what those environmental factors are is unclear, but one of the researchers, Dr. Lon White of the National Institute on Aging, speculated that they might include exposure to pesticides on Hawaiian plantations and the stress of moving from Japan to Hawaii. The research was reported in Wednesday's Journal of the American Medical Association.
Previous research into possible environmental causes has linked Alzheimer's with a low education level, excess zinc and serious head injuries, although some researchers have challenged those results.
The latest study involved 3,734 Japanese-American men who were enrolled in a heart study in the 1960s and tracked through the early 1990s. About 15 percent were born in Japan and moved at an early age to Hawaii. The rest were born in Hawaii to Japanese-born parents who left their homeland for a better life.
The participants were 71 to 93 years old, with an average age of 78. Alzheimer's was believed to be present in 5.4 percent of the subjects. That compared with a rate of 1.5 percent found in a recent Japanese study of 887 Hisayama residents 65 and older. Other Japanese studies have found similar rates, the researchers said.
"These observations lead us to speculate that environmental or cultural exposures associated with migration from Japan to Hawaii may have influenced the development" of Alzheimer's disease, White said.
Dr. David Bennett, associate director of Rush Alzheimer's Disease Center in Chicago, called the study provocative but flawed because it involved comparing studies that may have had different designs and methods.
CASTRO VALLEY, Calif. -- A judge has taken custody privileges away from the wife of an Alzheimer's patient who apparently overdosed on sleeping pills and whiskey. Dr. Gerald Klooster, who had been the subject of an intense nine-month custody battle, was in critical condition Wednesday, unconscious and breathing with the help of a ventilator, family members said. Superior Court Judge William McKinstry said if Klooster recovers, the couple's daughter, Kristen Hamstra, must take custody of him -- at least until a sheriff's investigation is completed.
In June, Klooster returned to the Castro Valley home he has shared with his wife, Ruth, for many years. He had been taken by his son, Chip Klooster, to live in Michigan. The custody dispute began after the younger Klooster learned his mother had contacted assisted-suicide advocate Dr. Jack Kevorkian about her ailing husband. Chip Klooster feared his father, a retired obstetrician, was being pushed into killing himself.
On Tuesday, Ruth Klooster told authorities she found her husband unconscious and slumped against a kitchen cabinet in his underwear and a bathrobe. Nearby were a bottle of whiskey, an empty 100-tablet medicine bottle labeled busitol sodium, a barbiturate, and a coffee cup with some whiskey in it.
''We're calling it an attempted suicide with suspicious circumstances,'' said sheriff's Lt. Dave Hoig. ''We're not pointing any fingers, but there are several unanswered questions, especially because of the family involved.''
Authorities will fingerprint the whiskey and medication bottles. But Hoig said that evidence would not necessarily indicate whether Klooster acted alone. Under California law, it is a felony to advise in an assisted suicide or even encourage it. Asked if her mother could have assisted in the overdose, Hamstra -- who sided with her mother in the custody dispute -- replied, ''Absolutely not. My mother is devastated.'' Chip Klooster, who has threatened to file a wrongful death suit if his father died suspiciously, said he was in shock. ''All I can say is 'I told everybody this was going to happen,' '' he said.
WASHINGTON - A new genetically modified mouse that mimics Alzheimer's disease should boost drug research and help scientists decipher the strange tangles of plaque in patients' brains, scientists said on Thursday. A report on the transgenic mice, which contain a human gene for an early-onset form of Alzheimer's, appears Friday in the journal Science.
"This is the first time anyone has shown this association between the plaques and the disfunctional learning and dementia in mice," said Dr. Karen Hsiao, the University of Minnesota neurologist who developed the mouse. An earlier transgenic mouse displayed some aspects of Alzheimer's, but according to researchers at the National Institutes of Health and the Chicago-bases Alzheimer's Association, both of which helped fund Hsiao's research, this one provides a more complete model for researchers.
Hsiao said in a telephone interview she will make the mouse widely available to academic researchers trying to understanding the heart-breaking disorder that robs patients of their memories and their independence. The University of Minnesota is also licensing the mouse to the Mayo Clinic, which through its Mayo Medical Ventures will sell the mice to pharmaceutical companies on a nonexclusive basis so that they can test compounds that could delay or conquer the disease, Hsiao said. A May spokesman was not immediately available to comment on the arrangement.
"There are a lot of compounds waiting to be tested and the pharmaceutical industry can use these mice," she said. "And academics can use it to try to understand what causes this disease." According to the Alzheimer's Association, the ailment afflicts more than 4 million Americans. Among them is former President Ronald Reagan. It is expected to become an even greater, and more expensive, problem as the baby boomers age.
There is no guarantee that a drug that works to slow down, or eventually even cure, Alzheimer's in mice will have the same effect in humans but scientists believe the transgenic rodent is an excellent model. In addition to being a testing ground for drugs, the genetically altered mice may also finally help scientists resolve the debate about the role of plaque in the brain -- whether plaque causes Alzheimer's or is a manifestation of it.
"We can't kill people to find out what is going on in their brain," said Hsaio, who suspects that something goes awry in the brain before formation of plaque. "The mice we can look at." Her lab worked with a long-lived hybrid mouse, injecting its eggs with a gene from a Swedish family with a history of early onset Alzheimer's. That gene directs production of a protein that forms the plaques.
The mice were tested against a control group in how well they learned to negotiate a water maze. Young mice performed well but as they aged, the transgenic mice showed more and more impairment, confusion and dementia. After death, the transgenic ones also displayed the plaque in the brain. Hsaio wants to now continue studying these patterns, examining the mice at closer intervals to get a better sense of when the plaque forms and the role it plays.