Alzheimer’s Disease: Connection with Rare Childhood Disorder

Alessandra d’Azzo PhD Department of Genetics, St Jude Children’s Research Hospital 262 Danny Thomas Place, Memphis, Tennessee 38105MedicalResearch.com Interview with:
Alessandra d’Azzo PhD
Department of Genetics, St Jude Children’s Research Hospital
262 Danny Thomas Place, Memphis, Tennessee 38105


MedicalResearch.com: What are the main findings of the study?

Dr. d’Azzo: We have discovered a connection between a rare childhood disorder and Alzheimer’s disease that usually affects older people.

The culprit is a metabolic enzyme called NEU1 that normally controls the recycling or disposal of proteins in a specific cell compartment, the lysosome.
When NEU1 is defective, children develop the severe metabolic disease, sialidosis.

Our study suggests that NEU1 also plays an important role in the development of Alzheimer’s disease. Based on this discovery, we decided to increase NEU1 enzyme activity in the brain of an Alzheimer’s disease mouse model that shows features characteristic of the human disease, namely the accumulation of toxic protein aggregates or plaques. Remarkably, we could significantly diminish the number of plaques in the brain of these mice by increasing NEU1 enzyme activity.

MedicalResearch.com: Were any of the findings unexpected?

Dr. d’Azzo: These findings were totally unexpected because we were studying a pediatric disease that, as it turns out, presents signs of premature aging, mimicking a severe and widespread condition in older people like Alzheimer’s disease.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. d’Azzo: This is the first time the NEU1 enzyme has been linked to Alzheimer’s disease. We hope that these findings can generate better tools to diagnose the disease and maybe slow down or even reverse disease progression.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. d’Azzo: We hope that these findings will propel Alzheimer’s disease research into areas that were not explored before, opening new avenues for the prevention or treatment of this devastating disease.

Citation:

Lysosomal NEU1 deficiency affects amyloid precursor protein levels and amyloid-β secretion via deregulated lysosomal exocytosis

Ida Annunziata, Annette Patterson, Danielle Helton, Huimin Hu, Simon Moshiach, Elida Gomero, Ralph Nixon, Alessandra d’Azzo

Nature Communications 4, doi:10.1038/ncomms3734  November 14 2013