Studies look at role of brain cell loss in movement disorder and early Alzheimer’s changes in patients with Down syndrome
Essential tremor linked to loss of Purkinje brain cells
Essential tremor (ET) is a common movement disorder affecting about 2% of the American population, and more than 20% of those over 90 years old. Despite its prevalence and decades of study, researchers don’t know the precise mechanisms underlying ET. Some research has suggested the brain’s cerebellum, responsible for coordinating voluntary movements, balance, and motor learning, gradually loses Purkinje cells (large neurons) and their cellular neighbors in ET patients. However, other studies haven’t shown this phenomenon.
To determine definitively whether these cells are lost, Elan Louis, M.D., M.S., Chair and Professor of Neurology and Investigator in the Peter O’Donnell Jr. Brain Institute at UT Southwestern Medical Center, worked with longtime collaborators at Columbia University Irving Medical Center to examine 452 postmortem brains. Among these specimens, 215 were donated over a 21-year period by patients who had ET, 165 were donated by healthy individuals, and 72 were donated by patients who had spinocerebellar ataxia, another movement disorder.
Their analysis, published in Annals of Clinical and Translational Neurology, showed that the ET patients had about 15% lower Purkinje cell density compared with the other groups, as well as significant loss of nearby cells. Discovering the cause of this loss could lead to new treatments for ET, the study authors said.
Other UTSW researchers who contributed to the study are Roberto Hernandez, Ph.D., Data Scientist, and Nora Hernandez, M.D., Manager of Research Programs.
Alzheimer’s changes appear early in patients with Down syndrome
Down syndrome is caused by an extra copy of chromosome 21. Because of genes present on this chromosome that are known to contribute to Alzheimer’s disease, patients with Down syndrome often develop the disease, sometimes at a relatively young age. However, few studies have examined Alzheimer’s-related pathological changes in the brains of people with Down syndrome, especially pediatric patients and those who are Black or Hispanic. Studies also hadn’t explored other neurodegenerative conditions in those with Down syndrome.
In a study published in the Journal of Alzheimer’s Disease, researchers led by a team at UT Southwestern examined 34 postmortem brains donated by patients with Down syndrome who underwent autopsies at UTSW between 1986 and 2023. They also incorporated findings from four previous studies, along with data from the National Alzheimer’s Coordinating Center (NACC), which collectively included an additional 126 brains from individuals with Down syndrome. The combined data encompassed a wide range of ages and races.
The findings showed that pathological changes associated with Alzheimer’s disease, such as amyloid plaques appearing as early as age 11 and tau tangles emerging by the mid-30s, were present in people with Down syndrome and increased with age, regardless of race. Other neurodegenerative conditions that frequently occur with Alzheimer’s disease were relatively rare in individuals with Down syndrome. These findings could help researchers develop unique diagnostic and therapeutic strategies for this population, the researchers concluded.
UTSW researchers who contributed to the study include first author Fatih Canan, M.D., Neuropathology fellow; Jack Raisanen, M.D., Professor of Pathology; Dennis Burns, M.D., Professor Emeritus of Pathology; Kimmo Hatanpaa, M.D., Ph.D., Professor of Pathology; Charles White III, M.D., Professor of Pathology and Director of Neuropathology and the Winspear Family Special Center for Research on the Neuropathology of Alzheimer's Disease; and senior author Elena Daoud, M.D., Ph.D., Assistant Professor of Pathology. Drs. Daoud and White are Investigators in the O’Donnell Brain Institute.