Altered protein glycosylation predicts Alzheimer's disease and modulates its pathology in disease model Drosophila

May 30, 2017Neurobiology of aging

Changes in protein sugar patterns may predict and influence Alzheimer's disease in a fruit fly model

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Many glycosylation-related genes are differentially expressed in the brains of Alzheimer’s disease patients compared to healthy controls.

Differences in gene expression were used to predict the occurrence of Alzheimer’s disease with high accuracy in a test cohort.
A set of key genes was identified whose expression is associated with the classification of Alzheimer's disease.
In a study using transgenic fruit flies that overexpress human tau, reducing the expression of homologs of 6 identified genes was investigated.
Three genes, OstDelta, l(2)not, and beta4GalT7, are associated with suppression of tauopathy, while pgnat5 and CG33303 may enhance tauopathy.
Specific alterations in protein glycosylation could play a role in the etiology of Alzheimer’s disease.

AI simplified

The pathological hallmarks of Alzheimer's disease (AD) are pathogenic oligomers and fibrils of misfolded amyloidogenic proteins (e.g., β-amyloid and hyper-phosphorylated tau in AD), which cause progressive loss of neurons in the brain and nervous system. Although deviations from normal protein glycosylation have been documented in AD, their role in disease pathology has been barely explored. Here our analysis of available expression data sets indicates that many glycosylation-related genes are differentially expressed in brains of AD patients compared with healthy controls. The robust differences found enabled us to predict the occurrence of AD with remarkable accuracy in a test cohort and identify a set of key genes whose expression determines this classification. We then studied in vivo the effect of reducing expression of homologs of 6 of these genes in transgenic Drosophila overexpressing human tau, a well-established invertebrate AD model. These experiments have led to the identification of glycosylation genes that may augment or ameliorate tauopathy phenotypes. Our results indicate that OstDelta, l(2)not and beta4GalT7 are tauopathy suppressors, whereas pgnat5 and CG33303 are enhancers, of tauopathy. These results suggest that specific alterations in protein glycosylation may play a causal role in AD etiology.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Altered protein glycosylation predicts Alzheimer's disease and modulates its pathology in disease model Drosophila

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief