Research scientists at Rosalind Franklin University and New York University are teaming up in an attempt to generate new therapeutic approaches to combat the onset of Alzheimer’s disease (AD) in individuals with Down syndrome (DS), the most common chromosomal disorder and cause of intellectual disability.

While individuals with DS are living longer, in part due to advances in medical science, more than 50-75% will develop dementia as they age, with many experiencing symptoms by their 40s, according to the National Institute on Aging. The institute has awarded Chicago Medical School investigator Grace Stutzmann, PhD, $1.8m— part of a $2.4m grant in collaboration with Stephen Ginsberg of NYU’s Grossman School of Medicine.

“We feel this is a powerful study that will greatly enlighten our understanding of how individuals with Down syndrome transition to Alzheimer’s through our combined strengths of transcriptomic analysis and neurophysiological mechanisms,” Stutzmann said.

A professor and director of RFU’s Center for Neurodegenerative Disease and Therapeutics, Stutzmann has long studied the early neuronal pathology that develops in AD.

Pathological hallmarks of AD include beta-amyloid and tau pathology, synaptic deficits, and neurodegeneration of key circuits underlying memory, attention and executive function. The extent to which these pathologies are found in DS are a significant component of the collaborative research project.

“While DS and AD phenotypes overlap in many respects,” according to Stutzmann and Ginsberg, “the extent of shared pathophysiological mechanisms remains poorly understood. The knowledge gap is a potentially missed opportunity to arrest the onset of AD dementia in DS.”

Stutzmann and RFU colleagues published a key AD paper in late 2022 in the scientific journal PNAS on “Protein mishandling and impaired lysosomal proteolysis generated through calcium dysregulation in Alzheimer’s disease,” which provides the groundwork for possible shared mechanisms with DS and aligns with differentially expressed gene pathways identified by Ginsberg in vulnerable cell types that underlie memory and executive function.

Ronald Kaplan, PhD, RFU executive vice president for research, commented: “We are pleased with Stutzmann’s collaboration with Ginsberg in studying the linkage of DS and AD patients with the goal of new therapeutic alternatives.”