Research

Cure Parkinson’s NZ-funded research leads to the first ever 3D visualization of human olfaction

November 21 2024

Olfactory dysfunction (loss of smell) is a very common early symptom of Parkinson’s disease, with >90% of people with Parkinson’s reporting (or being told they have it based on testing) this symptom. It is also relatively common (up to 20%) in the broader population, especially as we age, and is often seen in people with Alzheimer’s as well. But while not a highly specific marker of early Parkinson’s, when combined with other early symptoms (for example, REM sleep behaviour disorder) and new biological assays (detecting a pathological form of the protein alpha-synuclein), it is highly predictive of Parkinson’s and related diseases, often well before diagnosis. This has led to the compelling hypothesis that the disease originates in the nose and then moves into the brain over the course of many years.

Now imagine you are wanting to study the evolution of Parkinson’s disease from these very early stages, looking for pathological hallmarks (and opportunities to intervene) in the olfactory pathways of people with and without Parkinson’s, only to discover that the human olfactory system is not at all well understood, with most anatomical “maps” of the related structures being extrapolated from rodents. While it seems remarkable that, in the third decade of the 21^st Century, we would know more about the surface of Mars than what is up our noses, that was the reality faced by researchers at The University of Auckland’s Centre for Brain Research led by Professor Maurice Curtis. So, in typical Kiwi fashion, he and his team set about solving the 3D structures of the human olfactory system in order to better explore the early changes that occur in Parkinson’s disease.

This incredible piece of work, funded in part by Cure Parkinson’s NZ (we have funded Dr Victoria Low’s position for the last two years and are just commencing the third year of funding), has now culminated in a publication in the international journal Communications Biology. Displaying the patience of a Saint, Dr Low sliced thousands of very thin sections through donated human olfactory tissue, meticulously staining these sections with various chemicals that could help identify different cell types. A team of collaborators in Germany then scanned these sections using an automated microscope that could create digital images of the stained sections. With such a massive amount of data being generated, additional collaborators at the University of Auckland’s Bioengineering Institute then trained an artificial intelligence algorithm running on a supercomputer to create a virtual 3D model that you can watch from the comfort of your living room chair. (Tip: if you find yourself getting disorientated, you can reorient yourself by looking at the head image in the top-right corner).

The model, for the first time, gives us a deeper understanding of the structures involved in the human sense of smell, revealing that we have approximately 2.7 million sensory neurons up there, all projecting back to the brain via structures called “glomeruli”. Given that the nasal cavity is the site of entry for multiple infections, including SARS-CoV-2 (the virus causing Covid-19), as well as the site of exposure to numerous chemicals linked to Parkinson’s, the 3D model of the human olfactory system represents a hugely valuable tool that will aid in early diagnosis and understanding the mechanisms through which Parkinson’s first begins. Ongoing work, with expected publication in 2026, is investigating the presence of pathological forms of the protein alpha-synuclein in these structures, in people with and without Parkinson’s.

As Professor Curtis often says, “the dream is to be able to treat people who have a smell disorder and stop the spread of pathology to the brain, before it becomes a movement disorder” (which we recognize today as Parkinson’s.

We are immensely proud to have supported this work as understanding the brain region where Parkinson’s disease begins will be an important first step toward enabling early diagnosis and potentially preventing pathological proteins in this region of the brain from spreading to others.

The published article, which is titled Visualizing the human olfactory projection and ancillary structures in a 3D reconstruction, can be read or downloaded here.