Alzheimer’s disease (AD) is the most common dementia type, with no treatment to slow down the progression of this dehumanizing 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 the University of Eastern Finland shows astrocytes promote the decline of neuron function in AD. The team states 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 astrocytes are important cells in the brain, as they support neurons in many different ways. Astrocytes are responsible for many supportive roles in the brain such as energy production, pH balance, and regulating synapse 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 have on healthy neurons. Results show astrocytes in patients with AD produced significantly more beta-amyloid, a toxic protein known to accumulate in the brains of AD patients, than astrocytes in persons without AD.
Data findings show AD astrocytes secreted more cytokines, thought to mediate neuronal inflammation. Results show AD astrocytes also exhibit alterations in their energy metabolism likely leading to increased production of reactive oxygen species and reduced production of lactate, an important energy substrate for neurons. The lab states when astrocytes are co-cultured with healthy neurons, AD astrocytes cause significant changes in the signaling activity of neurons when compared to healthy-control astrocytes.
This team surmises their study shows some familial forms of AD are strongly associated with irregular astrocyte function. For the future, the researchers hypothesize astrocytes play a key role in the early stages of the disease, with changes in the function of these cells leading to neurodegeneration.
Source: University of Eastern Finland
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