Re-energising the brain: glucose metabolism, Tau protein and memory in ageing and dementia

Abstract

Memory naturally declines as we age, but the rapid loss of memory can be distressing for people living with Alzheimer’s disease (AD). How memories are formed and retrieved in the brain is not fully understood; it is thought to require plasticity to the synapses connecting neurons in a network of engram cells. Plasticity may occur either through changes to the volume and location of molecules and organelles within the synapse, or gross structural changes of synapses. Memory naturally declines as we age, as do many of the mechanisms required for learning and memory, such as changes in concentrations of the cytoskeletal structural protein Microtubule-Associated Protein Tau, reduced brain glucose metabolism, and sensitivities to insulin. The biggest risk factor for developing AD is ageing, yet only few studies try to reconcile the natural decline in functions we see with ageing with the dramatic impairment of these pathways in AD, such as Tau protein and energy homeostasis by neurons. This review will therefore explain the changes to metabolism, Tau protein, and memory impairment during ageing, and explore the latest research that links these processes to neurodegeneration seen in AD, and other Tauopathies. Understanding how ageing and dementia diverge may offer an important and underutilised avenue for therapeutic interventions to target metabolism in both “healthy” ageing and disease.