Sleep disturbances frequently emerge many years prior to the appearance of overt memory problems in Alzheimer’s disease. A new study suggests that the underlying cause of this pathology might be an excessive accumulation of the tau protein in the brain, which alters neuronal energy metabolism and keeps the brain in a perpetually excited state. This research was published in the journal npj Dementia.
In Alzheimer’s, the tau protein forms characteristic tangles within cells, damaging neurons and disrupting the transmission of signals between them, which leads to the impairment of memory and cognitive functions. However, scientists have discovered that its influence often manifests significantly earlier—at a stage where pronounced structural brain damage has not yet been detected.
A research team, guided by scientists from the University of Kentucky, managed to identify that pathological tau can “reallocate” the brain’s energy resources. Under normal conditions, neurons utilize glucose to generate energy. But when abnormalities linked to tau occur, a portion of this energy is diverted towards the accelerated synthesis of the neurotransmitter glutamate.
Glutamate is crucial for brain function, participating in learning and memory processes. Yet, its excess triggers overexcitation of neurons. Consequently, the brain becomes “stuck” in heightened activity, making it difficult to transition into deep sleep stages. The brain holds onto glucose, constantly converting it into glutamate, thereby sustaining the body in a wakeful state.
The experiments were conducted on mice. The scientists point out that disruptions in the energy exchange system occur even at the initial stages of tau dysfunction, preceding the formation of large protein aggregates. This explains why sleep issues are often detected long before the diagnosable symptoms of Alzheimer’s disease surface.
The researchers note that a vicious cycle sometimes forms between sleep disturbances and the disease. On one hand, the disease causes deterioration in sleep quality, and on the other, chronic sleep deprivation accelerates the progression of neurodegeneration.
The work’s authors believe that targeting drugs affecting brain metabolism presents a promising avenue. For instance, several medications used for epilepsy or type 2 diabetes reduce excessive neuronal activity and improve sleep.
What adds optimism is that some of these changes are reversible. The authors indicate that fully restoring normal sleep does not necessitate the complete elimination of all amyloid plaques and tau tangles in the brain.
Alzheimer’s disease is an intricate ailment linked to a variety of systemic dysfunctions. Therefore, effective therapy requires intervention across multiple mechanisms simultaneously. In the meantime, experts advise monitoring those risk factors that are within our control.
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