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Earlier treatment might be key in Alzheimer’s

Feb. 3, 2012
Courtesy of Columbia University Medical Center
and World Science staff

Sci­en­tists have long de­bat­ed wheth­er Alzheimer’s dis­ease starts in­de­pend­ently at dif­fer­ent times in dif­fer­ent brain ar­eas—or if it be­gins in one, and then spreads to con­nect­ed re­gions.

Re­search­ers have now an­nounced new find­ings that they say strongly sup­port the lat­ter the­o­ry about the dev­as­tat­ing, mem­o­ry-erasing ill­ness. They say an ab­nor­mal mol­e­cule known as tau—a key fea­ture of struc­tures known as “tan­gles” seen in Alzheimer’s pa­tients’ brains—seems to prop­a­gate along brain cir­cuits, “jump­ing” from cell to cell. 

The find­ings, pub­lished Feb. 1 in the on­line jour­nal PLoS One, open new av­enues to bet­ter un­der­stand and help cure Alzheimer’s and re­lat­ed dis­eases, said the stu­dy’s sen­ior au­thor, Ka­ren Duff of Co­lum­bia Uni­vers­ity Med­i­cal Cen­ter and the New York State Psy­chi­at­ric In­sti­tute.

The re­sults sug­gest “the most ef­fec­tive ap­proach may be to treat Alzheimer’s the way we treat can­cer—through early de­tec­tion and treat­ment, be­fore it has a chance to spread,” said Co­lum­bia re­search­er Scott Small, a co-au­thor of the stu­dy. “That is the ex­cit­ing clin­i­cal prom­ise down the road.”

Alzheimer’s, the most com­mon form of de­men­tia, is char­ac­ter­ized by the ac­cu­mula­t­ion of ab­nor­mal struc­tures in brain cells called neu­rons. Scientists describe these ab­norm­alities as as plaques and fi­brous tan­gles, both of which are made up of pro­tein mol­e­cules. Stud­ies have sug­gested the dis­ease, es­pe­cially the tan­gles, be­gins in the en­torhi­nal cor­tex, a part of the brain that plays a key role in mem­o­ry. Then the ab­nor­mal­i­ties ap­pear in an­a­tom­ic­ally linked, high­er brain re­gions.

“But these var­i­ous find­ings do not de­fin­i­tively show that Alzheimer’s spreads di­rectly from one brain re­gion to an­oth­er,” said Small.

The re­search­ers de­vel­oped a ge­net­ic­ally en­gi­neered mouse in which the ab­nor­mal, hu­man ver­sion of tau is pro­duced mainly in the en­to­rhi­nal cor­tex. As the mice aged, the de­formed pro­tein was seen to spread along a linked ana­tom­i­cal path­way. “This pat­tern very much fol­lows [what] we see at the ear­li­est stages of hu­man Alzheimer’s dis­ease,” said Duff.

The group al­so found ev­i­dence that the pro­tein was mov­ing from neu­ron to neu­ron across synapses, the junc­tions that these cells use to com­mu­ni­cate with each oth­er. So treat­ments could con­ceivably tar­get tau while it’s be­tween cells, added Duff. “If we can find the mech­an­ism by which tau spreads from one cell to anoth­er, we could po­ten­tially stop it from jump­ing across the syn­apses — per­haps us­ing some type of im­mu­noth­erapy.”


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Scientists have long debated whether Alzheimer’s disease starts independently at different times in different brain areas—or if it begins in one, and then spreads to connected regions. Researchers have now announced new findings that they say strongly supports the latter theory about the devastating, memory-erasing illness. They say an abnormal molecule known as tau—a key feature of abnormal structures known as “tangles” seen in Alzheimer’s patients’ brains—seems to propagate along linked brain circuits, “jumping” from cell to cell. The findings, published Feb. 1 in the online journal PLoS One, open new avenues to better understand and help cure Alzheimer’s and related diseases, said the study’s senior author, Karen Duff of Columbia University Medical Center and the New York State Psychiatric Institute. The results suggest “the most effective approach may be to treat Alzheimer’s the way we treat cancer—through early detection and treatment, before it has a chance to spread,” said Columbia researcher Scott Small, a co-author of the study. “That is the exciting clinical promise down the road.” Alzheimer’s, the most common form of dementia, is characterized by the accumulation of abnormal structures known as plaques and fibrous tangles, both made up of protein molecules, in brain cells called neurons. Studies have suggested the disease, especially the tangles, begins in the entorhinal cortex, a part of the brain that plays a key role in memory. Then the abnormalities appear in anatomically linked, higher brain regions. “But these various findings do not definitively show that Alzheimer’s spreads directly from one brain region to another,” said Small. The researchers developed a genetically engineered mouse in which the gene for abnormal human tau is activated mainly in the entorhinal cortex. As the mice aged, the abnormal human tau was seen to spread along a linked anatomical pathway. “This pattern very much follows the staging that we see at the earliest stages of human Alzheimer’s disease,” said Duff. The group also found evidence suggesting that the protein was moving from neuron to neuron across synapses, the junctions that these cells use to communicate with each other. Treatments could conceivably target tau while it’s between cells, added Duff. “If we can find the mechanism by which tau spreads from one cell to another, we could potentially stop it from jumping across the synapses — perhaps using some type of immunotherapy. This would prevent the disease from spreading to other regions of the brain, which is associated with more severe dementia.”