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Familial Alzheimer disease

Familial Alzheimer's disease (FAD) is an uncommon form of Alzheimer's disease that comes on earlier in life (usually between 30 and 60 years of age) and is inherited in an autosomal dominant fashion. While it only accounts for 5% or less of total Alzheimer's disease, it has presented a useful model in studying various aspects of the disorder. more...

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Clinical features

Alzheimer disease (AD) is the most common form of dementia. It usually occurs in old age, and starts gradually with early signs being forgetfulness, particularly in remembering recent events and the names of people and things. There may be some other cognitive difficulties early on, but nothing overly alarming.

As the disease progresses, the patient may start to exhibit greater problems. They may forget how to do simple things such as brushing their hair, and later in the disease may become anxious or aggressive, ultimately needing full-time care.

Familial Alzheimer disease is an uncommon form of Alzheimer's that comes on earlier in life (usually between 30 and 60 years) and is inherited in an autosomal dominant fashion. There are a number of types of familial (or early-onset) AD, which are identified by their genetics and other characteristics such as the age of onset. As a whole, this form of the disease only accounts for roughly 10% to 15% of all cases of AD.

Histologically, familial AD is practically indistinguishable from other forms of the disease. Deposits of amyloid can be seen in sections brain tissue (visible as an apple-green yellow birefringence under polarised light). This amyloid protein forms plaques and neurofibrillary tangles that progress through the memory centres of the brain. Very rarely the plaque may be unique, or uncharacteristic of AD; this can happen when there is a mutation in one of the genes that creates a functional, but malformed, protein instead of the ineffective gene products that usually result from mutations.

Genetic causes and mutations

There are multiple genetic causes of Alzheimer disease. Two of these are the presenilin polymorphisms on chromosomes 1 and 14, Others include several amyloid precursor protein polymorphisms and one of the four common alleles of apolipoprotein E. Several other gene polymorphisms have also been identified to increase susceptibility to Alzheimer's.

PSEN1 - Presenilin 1

The presenilin 1 gene (PSEN1) was linked to the long arm of chromosome 14 (14q24.3) using a pedigree of 34 people suffering from early-onset Alzheimer disease by Campion (1995). The actual gene was identified by Sherrington (1995) to be PSEN1, and multiple mutations were identified. Mutations in this gene cause familial Alzheimer's type 3. This protein has been identified as part of the enzymatic complex that cleaves amyloid beta peptide from APP (see below).

The gene contains 14 exons, and the coding portion is estimated at 60 kb, as reported by Rogaev (1997) and Del-Favero (1999). The protein the gene codes for (PS1) is an integral membrane protein. As stated by Ikeuchi (2002) it cleaves the protein Notch1 so is thought by Koizumi (2001) to have a role in somitogenesis in the embryo. It also has an action on an amyloid precursor protein, which gives its probable role in the pathogenesis of FAD. Homologs of PS1 have been found in plants, invertebrates and other vertebrates.

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Quantum Sufficit : Just Enough - American family life; exercise and gallbladder surgery risk; liver repair rate in light alcohol consumption; larger families
From American Family Physician, 5/1/00 by Jessica Greene

* Growing up in America might be harder than we think. According to a report in Time magazine, less than two thirds of American adolescent students reside with both of their parents. This number is shocking when compared with rates in other countries, such as Greece, where 91 percent of children live with both parents; the United States ranked next to last, only above Greenland. The study, done by the World Health Organization, revealed that U.S. youths are less likely to exercise and eat well than their foreign counterparts, but range in the middle with regard to drinking and are less likely to smoke or watch television for four or more hours a day.

* Exercise may be the stepping stone to fewer gallbladder surgeries. Women exercising just 30 minutes a day five times a week cut their risk by 20 percent, while physically active middle-aged men sliced their risk by almost 50 percent. Results of the ongoing Nurses' Health Study conducted at Harvard were first published in the New England Journal of Medicine. The exercise, which may improve body fat, insulin levels and high-density lipoprotein (HDL) cholesterol, could help cut the more than 800,000 hospitalizations related to gallbladder surgery that occur in the United States each year, states Consumer Reports on Health.

* There's a rat in my beer! A recent study at the University of Manitoba, Canada, showed that damaged livers in rats were repaired faster with light alcohol consumption than with no alcohol consumption, while heavy alcohol consumption was bad news. The trial studied the effect of light, moderate and heavy doses of alcohol in rats with partially removed livers. Researchers believe that light consumption of ethanol helps production of a repair-promoting gene. Animals receiving heavy doses of alcohol showed retardation of hepatic repair and those given moderate amounts of alcohol showed no extraordinary improvement reports Family Practice News.

* It's all in the family. A recent study indicates that persons from larger families are at a greater risk of developing Alzheimer's disease. According to statistics, the risk that an individual will have the disease increases by 8 percent for each additional sibling in a family and is 39 percent greater for those with five or more siblings than in those with less than five siblings. The report, first published in Neurology, suggests that the areas of the brain affected by the disease correspond with those that take the greatest amount of time to mature during child and teen years, and that's why childhood factors play a role in development of the disease.

* How precious is your time? According to recent projections by the U.S. Health Care Financing Administration, patients will spend around $1,172 a year on doctors' visits in 2005. This figure is more than 50 percent higher than the $563 that patients spent on doctors' visits in 1990, cites USA Today.

* Long menstrual cycles paired with high levels of psychologic distress may result in fertility problems, reports Family Practice News. A recent study at Aarhus (Denmark) University Hospital that included 393 couples wishing to conceive for the first time indicated that the odds ratio for pregnancy was much lower in women with cycle lengths of 35 days or more who had high levels of distress (ratio of 0.1) than in women with normal cycle lengths who had high levels of distress (ratio of 0.9). The odds ratio for pregnancy among all women in the high-distress group was 0.7.

* You're getting very sleepy--that is, if you are undergoing a nonemergency procedure at Harvard Medical School. According to a recent study reported in Internal Medicine News, Harvard doctors administered a simple form of hypnosis to patients undergoing angiography, angioplasty or kidney drainage and reduced the time of the procedures by an average of 17 minutes. The hypnotized patients proved more hemodynamically stable, had fewer complications and required less medication than those not undergoing hypnosis. Hypnosis also cut the cost of an average procedure by $130.

* Living on a prayer? Some heart patients at St. Luke's Hospital in Kansas City, Mo., just might be. A recent study at this hospital evaluated the effects of anonymous prayer on 1,000 heart patients. One half of the patients received prayer from a five-person team of Christians in addition to normal treatment, while others received just normal care. Patients who received prayer performed 10 percent better on a medical index of complications created for the study, according to the results published in the Archives of Internal Medicine. Although some researchers dispute the findings based on "chance," others credit prayer as having a "small but real effect" on subjects, reports U.S. News & World Report.

* How friendly is your office? For your overweight patients, it might not be friendly at all, suggests Internal Medicine News. A recent report lists ways that doctors can make their offices more accessible and productive for obese patients. Suggestions include replacing armchairs with couches or armless chairs, having scales that measure beyond 300 pounds and defining more reasonable weight loss goals. By adjusting your office setting and your approach slightly, you could see significant results in the weight loss of patients.

* The pitter-patter of little feet may cost health plans more than expected. Business & Health reports that it would only cost a health plan an average of $17 per worker per year to provide coverage for five major types of contraceptives. This cost is much lower than the estimated $542,000 per $1,000 spent on pregnancy-related absences of women and the $14,000 bill incurred to replace a woman who quits after giving birth. Only 48 percent of PPOs currently provide contraceptive coverage, and an estimated 48 percent of women between the ages of 15 and 44 have had one or more unplanned pregnancies.

* Sawing logs is dangerous for men and women, at least when it comes to cardiovascular risk, reports the American College of Cardiology. A recent study of 71,779 female nurses 40 to 65 years of age revealed that women who snore regularly have a 33 percent higher risk of heart attack or stroke than those who never snore. This risk factor was previously identified in men but until now was unexplored in women. The report, published in the Journal of the American College of Cardiology, additionally cites a 20 percent higher risk of heart attacks or stroke in women who snore only occasionally.

* Polishing those pearly whites may take off the extra pounds, suggests a contributor to The Physician and Sportsmedicine. The tip suggests that urging your patients to brush and floss their teeth after dinner may help them fend off evening snacking. The oral hygiene tricks serve well because toothpaste distorts the flavors of most foods and most persons would rather not perform the ritual again before they go to bed.

COPYRIGHT 2000 American Academy of Family Physicians
COPYRIGHT 2000 Gale Group

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