Dataset Information

A Review of Biomarkers for Alzheimer's Disease in Down Syndrome.

ABSTRACT: Down syndrome (Trisomy 21; DS) is a unique disease known to be associated with early-onset Alzheimer's disease (AD). The initial presentation of AD in DS is usually difficult to recognize, owing to the underlying intellectual disabilities. Using biomarkers as a prediction tool for detecting AD in at-risk people with DS may benefit patient care. The objective of this review is to discuss the utility of biomarkers in DS on the basis of the pathophysiology of the disease and to provide an update on recent studies in this field. Only through the comprehensive assessment of clinical symptoms, imaging studies, and biomarker analyses can people with DS who are at risk for AD be diagnosed early. Studies for biomarkers of AD in DS have focused on the common pathophysiology of AD in people with DS and in the general population. The most extensively studied biomarkers are amyloid and tau. Owing to the nature of amyloid precursor protein overproduction in DS, the baseline β-amyloid (Aβ) plasma levels are higher than those in controls. Hence, the changes in Aβ are considered to be a predictive marker for AD in DS. In addition, other markers related to telomere length, neuroinflammation, and methylation have been investigated for their correlation with AD progression. Future studies including different ethnic groups may be helpful to collect sufficient data to monitor drug safety and efficacy, stratify patients at risk for AD, and quantify the benefit of treatment.

SUBMITTER: Lee NC

PROVIDER: S-EPMC5520817 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:Down syndrome (DS), caused by chromosome 21 trisomy, is associated with an ultra-high risk of dementia due to Alzheimer's disease (AD), driven by amyloid precursor protein (APP) gene triplication. Understanding relevant molecular differences between those with DS, those with sporadic AD (sAD) without DS, and controls will aid in understanding AD development in DS. We explored group differences in plasma concentrations of amyloid-? peptides and tau (as their accumulation is a characteristic feature of AD) and cytokines (as the inflammatory response has been implicated in AD development, and immune dysfunction is common in DS). METHODS:We used ultrasensitive assays to compare plasma concentrations of the amyloid-? peptides A?40 and A?42, total tau (t-tau), and the cytokines IL1?, IL10, IL6, and TNF? between adults with DS (n =?31), adults with sAD (n =?27), and controls age-matched to the group with DS (n =?27), and explored relationships between molecular concentrations and with age within each group. In the group with DS, we also explored relationships with neurofilament light (NfL) concentration, due to its potential use as a biomarker for AD in DS. RESULTS:A?40, A?42, and IL1? concentrations were higher in DS, with a higher A?42/A?40 ratio in controls. The group with DS showed moderate positive associations between concentrations of t-tau and both A?42 and IL1?. Only NfL concentration in the group with DS showed a significant positive association with age. CONCLUSIONS:Concentrations of A?40 and A?42 were much higher in adults with DS than in other groups, reflecting APP gene triplication, while no difference in the A?42/A?40 ratio between those with DS and sAD may indicate similar processing and deposition of A?40 and A?42 in these groups. Higher concentrations of IL1? in DS may reflect an increased vulnerability to infections and/or an increased prevalence of autoimmune disorders, while the positive association between IL1? and t-tau in DS may indicate IL1? is associated with neurodegeneration. Finally, NfL concentration may be the most suitable biomarker for dementia progression in DS. The identification of such a biomarker is important to improve the detection of dementia and monitor its progression, and for designing clinical intervention studies.

Dataset Information

A Review of Biomarkers for Alzheimer's Disease in Down Syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets