Abnormalities in Brain Glucose Utilization and Its Impact on Cellular and Molecular Mechanisms in Sporadic Dementia of Alzheimer Type

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Abstract
Brain glucose utilization and ATP formation were found to be reduced to 54% and 81%, respectively, of control values in incipient sporadic dementia of Alzheimer type, causing reduced availability of the glucose-derived neurotransmitter acetylcholine. With respect to energy shortage, impacts on energy-dependent processes such as synaptic transmission, ion homeostasis, protein processing and degradation, extracellular transmission, and extracellular phosphorylation may be expected. Normal processing of the amyloid precursor protein was demonstrated to occur via a muscarinergic acetylcholine M1 and M3 receptor-mediated signal transduction pathway. Since both the muscarinergic acetylcholine receptors on pyramidal neurons and G proteins were found to be unaltered in DAT, the possibility is discussed that the diminution of glucose utilization and the energy shortage in DAT brain may contribute considerably to abnormal amyloid precursor protein processing and thus to secondary amyloid formation.