Down Syndrome and Alzheimer’s Disease

Individuals with Down syndrome have a high risk for Alzheimer’s disease, but little is known about the biomarkers that characterize disease onset and progression or why some individuals develop dementia much earlier than others. This study focuses on a longitudinal, multidisciplinary determination of key risk as well as protective biomarkers that are likely to affect Alzheimer’s disease progression. The following data will be collected: blood- and CSF-based measures of β-amyloid and tau proteins as well as protein, inflammatory, and lipid profiles; PET imaging of β-amyloid plaques and tau tangles; MRI imaging of gray matter atrophy, white matter abnormalities, and disruptions in intrinsic network connectivity; and polymorphisms in Alzheimer’s disease-related genes. In addition, demographic information, clinical assessments, and a neurocognitive battery will be collected to define mild cognitive impairment and dementia status and characterize progression in clinical status. Relationships among demographic, clinical, neuropsychological, blood, CSF, imaging, and genetic measures will be examined to develop the most valid indicators of preclinical and early stages of Alzheimer’s disease in individuals with Down syndrome. This can provide key insights into the pathways involved in Alzheimer’s disease progression and may allow for future therapeutic interventions before irreversible cognitive deterioration has occurred.

(National Institute on Aging, U01 AG051412-05)

Future Studies

The field of Alzheimer’s disease research in Down syndrome is relatively new. Therefore many relationships among demographic, clinical, neuropsychological, blood, CSF, imaging, and genetic measures have not yet been explored. Of particular interest may be investigating multiomic and genetic associations with more established Alzheimer’s disease biomarkers like CSF and PET measures of β-amyloid and tau proteins. In addition, a subset of participants have generously decided to donate their brain as part of their participation in the study. There will be opportunities to collaborate with the UCI MIND Neuropathology Core to analyze brain tissue samples from the UCI ADRC Tissue Repository in order to further our understanding of how antemortem biomarkers relate to neuropathology.

Impact

Developing Alzheimer’s disease biomarkers for people with Down syndrome will provide key insights into the pathways involved in Alzheimer’s disease progression in this population. These may be unique to Alzheimer’s disease in Down syndrome or common among all individuals who get Alzheimer’s disease. This research may also support enrollment of cognitively normal individuals at risk for Alzheimer’s disease in clinical trials, enabling the development of therapeutic interventions that act to stop the disease course before irreversible cognitive deterioration has occurred.

Soyun Kim, Ph.D.
Assistant Project Scientist

Mithra Sathishkumar
Imaging Analyst

Lisa Taylor
Neuroimaging Analyst