Written by Fazil Hussein: A new Alzheimer’s marker detectable in the blood up to ten years prior to diagnosis was announced in a recent article.
Alzheimer’s disease (AD) hits millions of patients worldwide. One major obstacle in drug development for AD is that treatment must be initiated at an early stage of the disease before irreversible neurodegeneration has occurred. Thus, biomarkers with good predictive value are important for selecting relevant populations for early interventions against the disease.
What is the new Alzheimer’s marker?
Bisecting N-acetylglucosamine (GlcNAc), a GlcNAc linked to the core β-mannose residue via a β1,4 linkage, is a special type of N-glycosylation that has been reported to be involved in various biological processes.
The bisecting GlcNAc is a common N-glycosylation motif, especially in the brain and has been found to be a common N-glycan structure on phosphorylated tau (p-tau) in AD. It was shown previously that the levels of this epitope were higher in the cerebrospinal fluid (CSF) of AD patients compared to non-demented controls. Moreover, its levels correlated with CSF levels of both total tau (t-tau) and p-tau proteins.
What did the researchers do?
A subsample of 233 participants who were free from dementia at baseline were randomly selected from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), an ongoing population-based longitudinal study. The original study population consists of 3363 randomly invited people 60 years of age or older living at home or in institutions in Kungsholmen, a district in central Stockholm. The follow-up assessments were performed every 6 years for participants 60 to 77 years of age and every 3 years for participants ≥78 years of age. The cohort was followed for a maximum of 17 years.
What did the researchers find about the new Alzheimer’s marker?
The blood levels of bisecting GlcNAc strongly correlated with blood t-tau levels, especially in individuals who later developed AD. Although neither tau nor bisecting GlcNAc on its own predicted AD, the tau/bisecting GlcNAc ratio significantly predicted progress to AD in individuals with intermediate tau/GlcNAc ratio. Combining tau/bisecting GlcNAc ratio with ApoE4 allele status further improved the prediction of AD.
Implications of the new Alzheimer’s marker
Based on the findings of this study, the researchers suggest that the tau/bisecting GlcNAc ratio should be explored and further validated as a blood biomarker for early prediction of AD. The earliest the disease is detected, the better the chances are for its treatment.
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