Possible Compensatory Events in Adult Down Syndrome Brain Prior to the Development of Alzheimer Disease Neuropathology: Targets for Nonpharmacological Intervention
Affiliations: [a] Institute for Brain Aging & Dementia, University of California, Irvine, CA, USA | [b] Department of Neurology, University of California, Irvine, CA, USA | [c] Department of Pediatrics, University of California, Irvine, CA, USA | [d] Eleanor Roosevelt Institute and the Department of Biological Sciences, University of Denver, Denver, CO, USA
Correspondence:
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Corresponding author: Elizabeth Head, Ph.D., Institute for Brain Aging & Dementia, Department of Neurology, University of California, 1259 Gillespie Neuroscience Research Facility, Irvine, CA, 92697-4540, USA. Tel.: +949 824 8700; Fax: +949 824 2071; E-mail: ehead@uci.edu
Abstract: Adults with Down syndrome (DS) develop Alzheimer disease (AD) pathology progressively with age but clinical signs of dementia are delayed by at least 10 years after the first signs of disease. Some individuals with DS do not develop dementia despite extensive AD neuropathology. Given the discordance between clinical decline and AD neuropathology, compensatory events may be of particular relevance for this group. Imaging studies using PET suggest compensatory increases in metabolic rate in vulnerable brain regions in DS prior to the development of dementia. Neurobiological studies of similarly aged DS autopsy cases provide further evidence of activation of plasticity mechanisms. Genes that are overexpressed in DS (APP, DSCAM, MNB/DYRK1A, and RCAN1) produce proteins critical for neuron and synapse growth, development and maintenance. We present the hypothesis that these genes may lead to developmental cognitive deficits but paradoxically with aging, may participate in molecular cascades supporting neuronal compensation. Enhancing or supporting compensatory mechanisms in aging individuals with DS may be beneficial as suggested by intervention studies in animal models. In combination, adults with DS may be a unique group of individuals well-suited for studies involving the manipulation or upregulation of compensatory responses as an approach to promote successful brain aging in the general population.
