Changes in the brains of deceased infants with Krabbe disease are similar to changes seen in dementia with Lewy bodies and Parkinson’s Disease

brain scan MRI

Researchers from Newcastle University have, for the first time, identified changes in the brains of deceased infants with Krabbe disease that are similar to those changes seen in dementia with Lewy bodies and Parkinson’s Disease.

Dr Daniel Erskine, Alzheimer’s Research UK Research Fellow at Newcastle University, who is an expert in Lewy bodies and led the study, said: ‘These findings challenge the view that changes to the brain that underlie these forms of dementia are merely age-associated.’

Krabbe disease is a rare, autosomal recessive, neurodegenerative childhood disorder arising in one in every 100,000 births, caused by a mutation in the Galactosylceramidase gene. The mutation results in the loss of the protective myelin nerve coating, with the disease typically resulting in death by the age of 2 years.

In both dementia with Lewy bodies and Parkinson’s disease, a protein called Alpha-synuclein builds up, creating Lewy bodies and resulting in nerve cell damage.

The research, published in the journal Brain, involved studying the postmortem brain tissue of four infants who died of Krabbe disease and comparing it with that of four infant controls. The researchers found widespread accumulations of Alpha-synuclein, a small protein abundant in the brain and found mainly in neuron presynaptic terminals, where it is believed to play a role in maintaining an adequate supply of synaptic vesicles.

Prion-like capacity 

To determine whether Alpha-synuclein in the brains of individuals with Krabbe disease displayed disease-associated pathogenic properties, the researchers evaluated its seeding capacity using the real-time quaking-induced conversion assay. 

The researchers said that they did not identify Lewy bodies in the brain tissue of infants with Krabbe disease; however, changes to Alpha-synuclein that are normally associated with dementia with Lewy bodies and Parkinson’s disease were present.

In particular, the researchers said that they found ‘aggregation into fibrils’ similar to those observed in Lewy body disease, ‘confirming the prion-like capacity of Krabbe disease-derived Alpha-synuclein.’ They highlighted that Alpha-synuclein protein in Krabbe disease-affected brain tissue was able to stick together and spread through the brain, a key change associated with dementia with Lewy bodies and Parkinson’s disease that is thought to drive the progression of both diseases.

This article originally appeared on Medscape, part of the Medscape Professional Network.


Lead image: sudok1/

Image 1: sudok1/