Scientists Find New Clues to Early Onset Alzheimer's

Too much plaque-building protein produced in people with certain genes, study finds

By Dennis Thompson

HealthDay Reporter

WEDNESDAY, June 12 (HealthDay News) -- People with genetic mutations that lead to inherited, early onset Alzheimer's disease overproduce a longer, stickier form of amyloid beta, the protein fragment that clumps into plaques in the brains of Alzheimer's patients, a small new study has found.

Researchers found that these people make about 20 percent more of a type of amyloid beta -- amyloid beta 42 -- than family members who do not carry the Alzheimer's mutation, according to research published in the June 12 edition of Science Translational Medicine.

Further, researchers Rachel Potter at Washington University School of Medicine in St. Louis and colleagues found that amyloid beta 42 disappears from cerebrospinal fluid much more quickly than other known forms of amyloid beta, possibly because it is being deposited on plaques in the brain.

Alzheimer's researchers have long believed that brain plaques created by amyloid beta cause the memory loss and thought impairment that comes with the disease.

This new study does not prove that amyloid plaques cause Alzheimer's, but it does provide more evidence regarding the way the disease develops and will guide future research into diagnosis and treatment, said Dr. Judy Willis, a neurologist and spokesperson for the American Academy of Neurology.

The mutation occurs in the presenilin gene and has previously been linked to increased production of amyloid beta 42 over amyloid beta 38 and 40, the other types of amyloid beta found in cerebrospinal fluid, the study said.

Earlier studies of the human brain after death and using animal research have suggested that amyloid beta 42 is the most important contributor to Alzheimer's.

The new study confirms that connection and also quantifies overproduction of amyloid beta 42 in living human brains. The investigators also found that amyloid beta 42 is exchanged and recycled in the body, slowing its exit from the brain.

"The amyloid protein buildup has been hypothesized to correlate with the symptoms of Alzheimer's by causing neuronal damage, but we do not know what causes the abnormalities of amyloid overproduction and decreased removal," Willis said.

The findings from the new study "are supportive of abnormal turnover of amyloid occurring in people with the genetic mutation decades before the onset of their symptoms," she said.

Researchers conducted the study by comparing 11 carriers of mutated presenilin genes with family members who do not have the mutation. They used advanced scanning technology that can "tag" and then track newly created proteins in the body. With this technology, they tracked the production and clearance of amyloid beta 40 and 42 in the participants' cerebrospinal fluid.

This research gives clinicians a potential "marker" to check when evaluating the Alzheimer's risk of a person with this genetic mutation, Willis said.

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Scientists ID Gene Behind Early Onset Puberty

Discovery could help children with 'central precocious puberty,' give insights to development

By Robert Preidt

HealthDay Reporter

WEDNESDAY, June 5 (HealthDay News) -- Scientists say they've identified a gene mutation behind a condition that causes children to undergo puberty before the age of 9.

The condition, known as central precocious puberty, appears to be inherited via a gene passed along by fathers, say researchers reporting online June 5 in the New England Journal of Medicine.

Besides helping children with central precocious puberty, "these findings will open the door for a new understanding of what controls the timing of puberty" generally, co-senior study author Dr. Ursula Kaiser, chief of the endocrinology, diabetes and hypertension division at Brigham and Women's Hospital in Boston, said in a hospital news release.

According to the authors, the mutation leads to the start of puberty before age 8 in girls and before age 9 in boys. That's earlier than the typical onset of puberty, which begins in girls between ages 8 and 13 and in boys between ages 9 and 14.

The study included genetic analyses of 40 people from 15 families with a history of early puberty. In five of the 15 families, the researchers discovered four mutations in the MKRN3 gene. A mutation in the MKRN3 gene can lead to premature activation of reproductive hormones and trigger early puberty, the study authors explained in the news release.

All of the people with the MKRN3 mutations inherited them from their fathers.

One expert who reviewed the research said the finding should be a great advance for children with central precocious puberty.

Testing children for the MKRN3 mutation "may help in the diagnosis, preventing the use of extensive testing and procedures such as MRI of the head," explained Dr. Patricia Vuguin, pediatric endocrinologist at Steven & Alexandra Cohen Children's Medical Center of New York, in New Hyde Park, N.Y.

She said better diagnostic tests would help spot patients at risk for early puberty and problems that often accompany it, such as short stature, psychological issues and other possible health issues. More generally, "the diagnosis will also help understand the role of this gene and other associated genes on how and when kids go into puberty, an area that is currently not clear," Vuguin said.

The findings will also be presented June 17 at the Endocrine Society's annual meeting.

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