DEVELOPMENTAL NEUROBIOLOGY | AUGUST 07, 2019
Petersen ME and O’Bryant S
Dev Neurobiol. 2019 Aug 7. doi: 10.1002/dneu.22714
ABSTRACT
Down syndrome (DS) occurs due to triplication of chromosome 21. Individuals with DS face an elevated risk for development of Alzheimer’s disease (AD) due to increased amyloid beta (Aβ) resulting from the over‐expression of the amyloid precursor protein found on chromosome 21. Diagnosis of AD among individuals with DS poses particular challenges resulting in an increased focus on alternative diagnostic methods such as blood‐based biomarkers. The aim of this review was to evaluate the current state of the literature of blood‐based biomarkers found in individuals with DS and particularly among those also diagnosed with AD or in prodromal stages (mild cognitive impairment [MCI]). A systematic review was conducted utilizing a comprehensive search strategy. Twenty‐four references were identified, of those, 22 fulfilled inclusion criteria and were selected for further analysis with restriction to only plasma‐based biomarkers. Studies found Aβ to be consistently higher among individuals with DS; however, the link between Aβ peptides (Aβ 1‐42 and Aβ 1‐40) and AD among DS was inconsistent. Inflammatory based proteins were more reliably found to be elevated leading to preliminary work focused on an algorithmic approach with predominantly inflammatory based proteins to detect AD and MCI as well as predict risk of incidence among DS. Separate work has also shown remarkable diagnostic accuracy with the use of a single protein (NfL) as compared to combined proteomic profiles. This review serves to outline the current state of the literature and highlight potential plasma‐based biomarkers for use in detecting AD and MCI among this at‐risk population.
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