The genetic disease Huntington’s not only affects nerve cells in the brain but also has widespread effects on microscopic blood vessels according to research.

These changes to the vasculature were also observed in the pre-symptomatic stages of the disease, demonstrating the potential for this research for predicting brain health and evaluating the beneficial effects of lifestyle changes or treatments.

Huntington’s disease is an inherited genetic condition leading to dementia, with a progressive decline in a person’s movement, memory, and cognition. Individuals with ≥40 cytosine–adenine–guanine repeats on the interesting transcript 15 gene develop Huntington’s disease due to a mutated huntingtin protein. While the associated structural and molecular changes are well characterized, the alterations in neurovascular function that lead to the symptoms are not yet fully understood. There is currently no cure.

The study, published in the journal Brain Communications.

The team investigated changes in the coordination between neuronal activity and the brain’s oxygenation in Huntington’s disease.

The vasculature and brain work together to ensure that the brain receives sufficient energy. In fact, the brain needs as much as 20% of the body’s energy consumption despite only weighing approximately 2% of the body’s weight.

The “neurovascular unit” consists of vasculature connected via brain cells called astrocytes to neurons and ensures that this cooperation is successful.

To assess the function of these neurovascular units, the researchers combined non-invasive measurement techniques and novel analysis methods developed.

Probes emitting infrared light were placed on the heads of participants in the study. The infrared light penetrated the skull harmlessly and enabled researchers to measure the brain’s blood oxygenation.

Electrodes, which can measure electrical activity from neurons, were also placed on the heads of participants. The researchers then studied the many rhythms related to the functioning of the brain and the cardiovascular system using mathematical techniques.  These rhythms included the heart and respiration rates, related to the transport of nutrients and oxygen, as well as slower rhythms associated with local control of blood flow. Brain activity manifests in faster rhythms.

Efficient functioning of the brain depends on how well all these rhythms are orchestrated. To assess the efficiency of the neurovascular unit, both the strength and the coordination of these rhythms were assessed by computing their “power” and “phase coherence”.

The researchers show a reduced efficiency of the neurovascular unit in Huntington’s disease both in the presymptomatic and symptomatic stages of the disease. The vasculature is already significantly impaired in the presymptomatic stage of the disease, resulting in reduced cerebral blood flow control. The results indicate vascular remodelling, which is most likely a compensatory mechanism. In contrast, the declines in α and γ coherence indicate a gradual deterioration of neuronal activity.

The senior author said: “We are hopeful that the method described could be used to monitor the disease progression and to evaluate the effect of potential treatments or lifestyle changes in Huntington’s disease and other neurodegenerative diseases. We also hope that our study will stimulate new treatments of Huntington’s disease targeting the vasculature and brain metabolism.”

https://academic.oup.com/braincomms/article/6/3/fcae166/7689585

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