Astrocytes linked to Alzheimer’s disease for the first time.
Alzheimer’s disease (AD) is the most common dementia type, with no treatment to slow down the progression of the disease currently available. The mechanisms of AD are poorly understood with drug therapy focused on restoring the normal function of neurons and microglia. Now, a study from researchers at University of Eastern Finland shows that astrocytes promote the decline of neuron function in AD. The team state that this is the first time a direct association between astrocytes and AD has been shown. The opensource study is published in Stem Cell Reports.
Previous studies show that astrocytes are important brain cells, as they support neurons in many different ways. Astrocytes are responsible, for example, for the energy production of the brain, ion and pH balance, and they regulate synapse formation, the connections between neurons. Although most studies have focused on neuronal cells, astrocytes have also been suggested to contribute to AD pathology. The current study identifies an important role for astrocytes in AD pathology and highlights the strength of Induced Pluripotent Stem Cell (iPSC)-derived models for brain diseases.
The current study compares differentiated astrocytes from familial AD patients carrying a mutation in the presenilin 1 gene to astrocytes from healthy donors, and the effects of these cells on healthy neurons. Results show that astrocytes in patients with AD produced significantly more beta-amyloid, a toxic protein which is known to accumulate in the brains of AD patients, than astrocytes in persons without AD.
Data findings show that AD astrocytes secreted more cytokines, which are thought to mediate neuronal inflammation. Results show that AD astrocytes also exhibit alterations in their energy metabolism which likely leads to increased production of reactive oxygen species and reduced production of lactate, an important energy substrate for neurons. The lab state that when astrocytes are co-cultured with healthy neurons, AD astrocytes cause significant changes on the signalling activity of neurons when compared to healthy-control astrocytes.
This team surmise their study shows some familial forms of AD are strongly associated with irregular astrocyte function, which promotes brain inflammation and weakens neurons’ energy production and signalling. For the future, the researchers hypothesize it could be shown that astrocytes play a key role in the early stages of the disease and changes in the function of these cells lead to neurodegeneration.