In many people an early indicator of Huntington’s disease are changes to their smell or olfaction. The process of olfaction works through structures in our nose known as the nasal pathway, and in our brain known as the olfactory system. The main proponents to this system are the olfactory bulbs, which are neural structures that receive smell information and send it to other regions of the brain to be processed.
Figure shows the location of the nasal cavity and olfactory bulb. Image created in BioRender.com.
Interestingly, olfactory dysfunctions are also common in other neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. The causes of these olfactory dysfunctions are unknown, although clues may lie in the clumping (or aggregation) of different proteins which are thought to be toxic to the brain. Aggregates of β-amyloid and tau proteins have been found in the olfactory bulb of individuals with Alzheimer’s disease, whilst aggregates of α-synuclein protein have been found in the olfactory bulb of people with Parkinson’s disease. However, although mutant huntingtin protein (mHtt) aggregates have been found in other areas of the brain of people with Huntington’s disease, it is unknown as to whether they also affect the olfactory bulb. The presence of mHtt aggregates in other brain regions is important as they may contribute to the loss of neurons and subsequently the symptoms seen in Huntington’s disease. A study, performed at the Centre for Brain Research in Auckland, New Zealand aimed to investigate whether these potentially toxic mHtt aggregates could be also found in the olfactory bulb of people with Huntington’s disease.
Glossary
α-synuclein – Found in aggregated forms known as Lewy bodies in the Parkinson’s disease brain.
Anterior olfactory nucleus (AON) – The olfactory bulb is split into main two regions, the anterior and posterior, both containing different neural circuitry. The AON is usually the region of the olfactory bulb where the aggregates form in Alzheimer’s and Parkinson’s disease.
β-amyloid – Found in aggregated forms known as β-amyloid plaques in the Alzheimer’s brain.
Mutant Huntingtin protein (mHtt) – A mutated form of the polyQ gene resulting in an expanded CAG repeat in the gene sequence found in individuals with Huntington’s disease. The presence of mHtt aggregates results in cell dysfunction which is toxic to the brain ultimately resulting in Huntington disease symptoms.
Tau – Found in aggregated forms known as hyperphosphorylated tau tangles in the Alzheimer’s brain. The presence of tau tangles results in Alzheimer’s symptoms.
This study investigated thirteen brains from Huntington’s cases and five neurologically healthy cases, referred to as control cases. All human brain tissue was kindly donated to the Neurological Foundation Human Brain Bank. The experiment consisted of staining the olfactory bulbs in order to visualise the mHtt aggregates. These sections were imaged and then analysed to determine the difference in the amount of mHtt aggregates between control and Huntington’s disease cases. In the experiments performed, there were no mHtt aggregates found within the olfactory bulb of any control cases. In comparison, in the Huntington’s cases, there were mHtt aggregates found in many regions of the olfactory tract, the majority of which was found in a particular part of the olfactory bulb known as the anterior olfactory nucleus (AON).
This is an exciting finding as it suggests that the mHtt aggregates in the olfactory bulbs, especially in the AON, could cause olfactory dysfunction in the brains of people with Huntington’s disease. These dysfunctions may be responsible for the problems with smell which can often be observed in preclinical and clinical Huntington’s. This may give us greater insight as to what is happening to the brain in early in the disease, as olfactory dysfunction is usually a preclinical or early sign of Huntington’s disease. Being able to detect these symptoms early allows for the possibility of an early treatment being able to be administered.
Original research article: Huntingtin Aggregates in the Olfactory Bulb in Huntington’s Disease, Highet et al 2020
Author
Star Thai
Star is a lab technician at the Centre for Brain Research at the University of Auckland, her current focus the auditory cortex in Alzheimer’s disease. She received her master’s degree specializing in looking at the neurochemistry in Huntington’s and Parkinson’s disease. She is highly passionate about neuroscience and the pursuit of learning more about neurodegenerative diseases.
Editor
Jessica Crockett
Jessica has recently obtained a Masters of Science after spending a year in the Centre for Brain Research (CBR) at the University of Auckland completing her thesis. She has a passion for research and is currently working as a research technician at the CBR on an exciting new project investigating the neuropathology of X-linked Dystonia Parkinsonism, a neurodegenerative disease endemic to the Philippines. She values the importance of sharing scientific knowledge and hopes to help do this in an accessible way.
