Alzheimer’s disease triggers memory and learning disorders. To date, the causes are poorly understood. Now, researchers of the German Center for Neurodegenerative Diseases (DZNE) are shedding light on a possible mechanism.
Usually, during learning existing connections between neurons are modified and new ones created. Indeed, the researchers observed such changes happening at the interneurons of the healthy mice. However, in the rodents that exhibited symptoms of Alzheimer’s, cellular wiring was disturbed and connections were not established in some cases. Besides, these mice had problems to recognize their training environment.
What caused the faulty wiring? The researchers found out that this effect was triggered by the loss of a specific set of cellular connections that normally reach out to the interneurons. "Already in the early stages of Alzheimer’s cholinergic projections degenerate. Their name derives from the fact that they release a neurotransmitter called ‘acetylcholine’," Fuhrmann says. "Some of these connections usually link up to the interneurons we investigated. When they get lost this has direct impact on the interneurons. Their cellular wiring becomes dysfunctional, which impairs their ability to inhibit others cells."
It has long been suspected that memory decline associated with Alzheimer’s may be caused by the loss of cholinergic projections. Reduction of these cellular contacts leads to a deficiency of acetylcholine. Hence, one treatment approach is to counteract the shortage of the neurotransmitter through medication, which turned out to be not successful on the long-term. However, the current work elucidates how acetylcholine might be related to memory function on the cellular level. "Our study now points to a mechanism that may be relevant for humans. The loss of cholinergic connections impairs the regulating ability of hippocampal interneurons. This worsens memory performance," Fuhrmann explains. "Looking ahead, these findings could help to develop drugs to treat memory problems caused by Alzheimer’s more effectively than it is possible today."
REHACARE.com; Source: DZNE