New information on the early stages of dementia with Lewy bodies

by  University of Helsinki

Olfactory bulb/peduncle alpha-synuclein staining predominance categorized by LRP progression-based classification [6]. Percentages add up to 100% within each LRP progression-based classification category, meaning all the caudo-rostral cases equal 100% spread across negative, peripheral and anterior olfactory nucleus predominance for alpha-synuclein staining. Similarly, the amygdala-based category cases add up to 100% spread across the peripheral and anterior olfactory nucleus predominance for alpha-synuclein staining (there were no amygdala-based cases that were negative in olfactory bulb/peduncle alpha-synuclein staining). When comparing these groups, age and sex adjusted p value < 0.001. Credit: DOI: 10.1007/s00401-021-02364-6

Results obtained in a study recently completed at the University of Helsinki and Helsinki University Hospital reinforce the notion that dementia with Lewy bodies can be pathologically classified into two different disease types.

Dementia with Lewy bodies is the second most common neurodegenerative disease after Alzheimer’s disease, and it affects millions of people globally. This type of progressive memory disorder has features associated with both Alzheimer’s disease and Parkinson’s disease.

At the tissue level, accumulations known as Lewy bodies that contain the alpha-synuclein protein, are found in the limbic system of the brain, in the cerebral cortex and the brainstem.

Two years ago, researchers at the University of Helsinki and Helsinki University Hospital demonstrated that pathological changes of dementia with Lewy bodies occur in two different forms. In the more common form of the disease, changes progress upwards from the brainstem, while those associated with the other disease type originate in the amygdala.

Now, the researchers have advanced their investigations further.

“We continued our studies, focusing on the olfactory bulb in the brain. The olfactory bulb is considered one of the first brain regions where alpha-synuclein accumulations relating to dementia with Lewy bodies occur,” says Liisa Myllykangas, a neuropathologist and clinical instructor.

In the follow-up study, the researchers utilized a unique Finnish population-based neuropathological dataset (N=291). Alpha-synuclein accumulations in the olfactory bulb have not previously been investigated in non-selected population datasets.

Based on the results, two patterns of accumulations can be identified in the olfactory bulb, with differences seen in their anatomical location and severity.

“Comparing the findings with the two types of dementia with Lewy bodies defined in our prior study, we noted that the different alpha-synuclein accumulation patterns in the olfactory bulb have a strong association with these two disease types,” Myllykangas says.

The results support the view that the first changes caused by dementia with Lewy bodies take place in the olfactory bulb in persons whose disease progresses to the amygdala and the rest of the limbic system at an early stage. In contrast, the onset of the other disease type occurs in the brainstem, spreading later to the olfactory bulb. The findings reinforce the notion that dementia with Lewy bodies can be classified into two different disease types.