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Microcolumns In Brain Disrupted In Alzheimer's Disease

Vertical structures called microcolumns, found in the cerebral cortex of normal brains, are disrupted in the brains of people affected by Alzheimer's disease, report Boston University scientists in the cover story of today's issue of the Proceedings of the National Academy of Sciences.

"These structures, normally found in the cerebral cortex -- the six-layered portion of the human brain that controls higher functions such as rational thought and speech -- may hold the key to understanding, and perhaps reversing, the ravages of this devastating disease," says H. Eugene Stanley, co-senior author and director of Boston University's Center for Polymer Studies.

The team of physicists, working on tissue samples supplied by Bradley Hyman, director of the Alzheimer's Research Unit at Massachusetts General Hospital, developed a novel imaging technology based on statistical physics to visualize and analyze brain tissue.

They compared the brains of subjects stricken with Alzheimer's disease (AD) and a related condition known as Lewy body dementia (LBD) with those from control subjects.

The new imaging technique revealed microcolumns -- chains of about 11 neurons linked together like the segments of a snake -- running perpendicularly through the levels, or laminae, of the cerebral cortex in normal subjects.

"In LBD we saw practically no such microcolumns," says lead author Sergey Buldyrev, "and in AD the columns were much smaller and less pronounced than in the controls."

Microcolumns have been believed to play a role in brain function for some time, but this is the first time they have been quantified and compared in normal and diseased brains. Furthermore, the study revealed that the absence of microcolumns is in direct proportion to the number of fibrillary tangles in the brain, but not related to the number of senile neuritic plaques.

Tangles and plaques are the two primary changes in brain tissue that are believed to be causally related to the death of brain cells that characterizes Alzheimer's.

"We found that in AD and LBD disease, the microcolumn organization is disrupted -- and this disruption may correlate with cognitive impairment," says Buldyrev. "This finding is consistent with the fact that in AD, roughly half of the neurons are lost in the disease, making it very likely that any organization in the brain would be lost as well.

"In LBD, however, only 10 percent or fewer of the neurons are lost -- and yet it still appears that there is a dramatic absence of microcolumns. This disruption of the microcolumnar organization is surprising and leads us to surmise that the loss of vertical organization is connected to the cognitive loss in these diseases."

The imaging technique relies on methods developed in the field of statistical physics for the study of liquids and crystals. It involves developing a centered density matrix for the area around each neuron in a tissue image and averaging the results for many neurons to calculate a statistically average environment for a typical neuron.

This allows the scientists to magnify tiny features of the neuronal architecture, such as microcolumns. The technique may also someday be applied to study tissue changes in other neurological diseases, such as schizophrenia. - By Joan Schwartz

(Editor's Note: Images can be found at this website.)

[Contact: Joan Schwartz]






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