Albert Gjedde, Professor
The purpose of the Brain Theme Group at the Department of Nuclear Medicine is to provide the infrastructure for tests of a chain of hypotheses that link several mechanisms into a single concept of healthy and unhealthy brain aging with progression to neurodegeneration. The hypotheses underlying the work include the claims that
1) both brain energy metabolism measured as glucose metabolism and the accompanying aerobic glycolysis rates decline in healthy aging in association with age-dependent formation of misfolded proteins with decline of glucose metabolism, to a point when the aging is no longer healthy;
2) reductions of regional cerebral glucose metabolism associated with decreased aerobic glycolysis are consequences of insulin resistance in the aging brain that block both glucose metabolism and dopaminergic neurotransmission, and eventually lead to unhealthy aging; and
3) disruption of dopaminergic neurotransmission affects dendritic spine density that is known to depend on the intensity of dopaminergic neurotransmission, to an extent that coincides with the onset of unhealthy aging.
To test the hypotheses, the workers at the Brain Theme Group employ combined positron emission tomography (PET), magnetic resonance imaging (MRI), and magnetic resonance spectrometry (MRS) to measure and correlate changes of brain glucose metabolism, lactate generation and consumption, misfolded protein deposition, insulin resistance, dendritic spine density, and dopaminergic activity in wide age ranges of human volunteers and groups of patients with neurodegenerative or neuropsychiatric disorders. The collaborators at the Brain Theme Group take advantage of the newly installed state-of-the-art PET-MR system at the Department of Nuclear Medicine that provides measures of all of the listed physiological variables.
To carry out the investigations, the workers at the Brain Theme Group have designed a series of studies to reveal correlations among the separate measures of energy metabolism, misfolded protein deposition, insulin resistance, dopamine turnover, and dendritic spines density in healthy and unhealthy aging. The correlations among changes of these physiological and pathological factors in brain aging never previously have been identified jointly in groups of healthy volunteers and patients at different stages of healthy and unhealthy aging. The tests include a series of investigations in which the collaborators at the Brain Theme Group focus on the mildly cognitively impaired (MCI) and Alzheimer’s disease (AD) patients, to identify the key events that turn healthy brain aging into pathological aging.