Cerebrospinal fluid biomarkers of Alzheimer's disease in a cohort of adults with Down syndrome

Abstract

Introduction Virtually all individuals with Down syndrome (DS) will develop Alzheimer's disease (AD) pathology by age 40. Cerebrospinal fluid (CSF) biomarkers have characterized AD pathology in cohorts of late‐onset AD (LOAD) and autosomal‐dominant AD (ADAD). Few studies have evaluated such biomarkers in adults with DS. Methods CSF concentrations of amyloid beta (Aβ)40, Aβ42, tau, phospho‐tau181 (p‐tau), neurofilament light chain (NfL), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase‐3‐like protein 1 (YKL‐40), alpha synuclein (αSyn), neurogranin (Ng), synaptosomal‐associated protein 25 (SNAP‐25), and visinin‐like protein 1 (VILIP‐1) were assessed in CSF from 44 adults with DS from the Alzheimer's Biomarker Consortium–Down Syndrome study. Biomarker levels were evaluated by cognitive status, age, and apolipoprotein E gene ( APOE ) ε4 carrier status. Results Biomarker abnormalities indicative of amyloid deposition, tauopathy, neurodegeneration, synaptic dysfunction, and neuroinflammation were associated with increased cognitive impairment. Age and APOE ε4 status influenced some biomarkers. Discussion The profile of many established and emerging CSF biomarkers of AD in a cohort of adults with DS was similar to that reported in LOAD and ADAD, while some differences were observed.

Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer’s disease in adults with Down syndrome

“…We and others have described the usefulness of cerebrospinal fluid (CSF) and amyloid positron emission tomography (PET) biomarkers to detect the core neuropathological hallmarks of AD in this population [5][6][7][8] . All these studies support the notion that AD in DS recapitulates the pattern observed in both sporadic and autosomal-dominant AD.…”

Significance of Blood and Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: Sensitivity, Specificity and Potential for Clinical Use

“…Aprioristic analysis of CSF and blood by metabolomic, proteomic, lipidomic and other large-scale approaches could be the key, if done early enough in the pathogenic course, to generate hypothesis on the primordial triggers of the disease, besides to identify AD patients and predict their trajectory. In this respect, autosomal dominant families and patients with Down’s syndrome [ 134 , 349 , 350 ] may be the ideal subjects for dedicated longitudinal studies.…”

“…A recent study in a Down syndrome (DS) cohort [ 134 ], with CSF sampling from age 30 to 61, showed Aβ42 reductions which was proportional to age and cognitive decline (from cognitive stable, to MCI to AD), with higher levels than those reported in corresponding older non-DS controls, MCI and AD [ 135 ], but did not have a non-DS age-matched control group. In another study [ 136 ], CSF levels of Aβ peptide were found to be elevated from 8 to 54 months of age in DS children, while tau was low, likely due to Aβ overproduction in the absence of significant parenchymal sequestration and neuronal loss at that age.…”

Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer’s Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study

“…Biomarker Assays 2.3.1. Plasma P-tau Assays Both p-tau181 and p-tau217 levels were measured in duplicate by electrochemiluminescence using a proprietary assay developed by Lilly Research Laboratories as previously described [25][26][27]34,[39][40][41]. Briefly, samples were diluted 1:2 and 50 µL of diluted sample was used for each replicate.…”

“…Recent data from the multi-site Alzheimer’s Biomarker Consortium–Down Syndrome (ABC-DS) cohort ( n = 44) showed that the CSF AD biomarker profiles are very similar to LOAD and AD-AD [ 25 ]. The study showed that individuals with AD dementia had low CSF Aβ 1–42 and Aβ 42 /Aβ 40 ratio, indicative of amyloid deposition; increased p-tau, denoting the presence of neurofibrillary tangles [ 26 , 27 , 28 ]; and increased total tau and neurofilament light chain (NfL), indicating neurodegeneration [ 25 ]. The ABC-DS study findings are consistent with the results from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) cohort in Europe [ 29 ].…”