Damage in Down Syndrome, Alzheimer's Have Common Link
Studies show neurodegeneration in both diseases may be due to faulty neurotrophin pathway
FRIDAY, July 7 (HealthDay News) -- The neuronal degeneration observed in both Down syndrome and Alzheimer disease may be due to defects in the neurotrophin signaling pathway, according to two reports in the July 6 issue of Neuron.
In the first report, Susan Dorsey, Ph.D., R.N., from the National Cancer Institute in Frederick, Md., and colleagues used a mouse model of trisomy 21 (mice with trisomy 16) to show that increased gene dosage of a truncated neurotrophin receptor found on the trisomic chromosome is primarily responsible for the nerve cell death associated with disease. By reducing its expression using gene targeting, the researchers could reduce cortical neuron death to normal levels.
In another mouse model of trisomy 21, Ahmad Salehi, M.D., Ph.D., from Stanford University in Stanford, Calif., and colleagues showed that increased dosage of the Alzheimer disease-related amyloid precursor protein gene, App, hinders intracellular trafficking nerve growth factor and causes degeneration of basal forebrain cholinergic neurons. The extent of nerve cell death was dependent on the dose of App.
"The papers provide interesting insights into the pathophysiology of Down syndrome and underline the notion that the primary aim of treatment of neurodegenerative disorders is not to keep neurons alive but to keep them connected," write Eero Castren and Heikki Tanila of the University of Helsinki, Finland, in an accompanying editorial.