Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer's disease: a multicenter study

Abstract

In this report, we present the results of a multicenter study to test analytic and diagnostic performance of soluble forms of amyloid precursor proteins a and b (sAPPa and sAPPb) in the cerebrospinal fluid (CSF) of patients with different forms of dementing conditions. CSF samples were collected from 188 patients with early dementia (mini-mental state examinationX20 in majority of cases) and mild cognitive impairment (MCI) in 12 gerontopsychiatric centers, and the clinical diagnoses were supported by neurochemical dementia diagnostic (NDD) tools: CSF amyloidb peptides, Tau and phospho-Tau. sAPPa and sAPPb were measured with multiplexing method based on electrochemiluminescence. sAPPa and sAPPb CSF concentrations correlated with each other with very high correlation ratio (R = 0.96, P < 0.001). We observed highly significantly increased sAPPa and sAPPb CSF concentrations in patients with NDD characteristic for Alzheimer's disease (AD) compared to those with NDD negative results. sAPPa and sAPPb highly significantly separated patients with AD, whose diagnosis was supported by NDD findings (sAPPa: cutoff, 117.4 ng ml À1 , sensitivity, 68%, specificity, 85%, P < 0.001; sAPPb: cutoff, 181.8 ng ml À1 , sensitivity, 75%, specificity, 85%, P < 0.001), from the patients clinically assessed as having other dementias and supported by NDD untypical for AD. We conclude sAPPa and sAPPb might be regarded as novel promising biomarkers supporting the clinical diagnosis of AD.

Altered Concentrations of Amyloid Precursor Protein Metabolites in the Cerebrospinal Fluid of Patients with Bipolar Disorder

“…By contrast, high plasma concentrations of sAPP-a have been reported in autistic patients (Bailey et al, 2008;Ray et al, 2011). In Alzheimer's disease, both unaltered and elevated concentrations of sAPP-a and sAPP-b have been reported (Lewczuk et al, 2010;Perneczky et al, 2011;Rosen et al, 2012).…”

Fluid Biomarkers in Alzheimer Disease

“…In sporadic AD and MCI, CSF levels of both sAPPa and sAPPb are unaltered or slightly increased (Olsson et al 2003;Zetterberg et al 2008;Lewczuk et al 2010). Although there is no consistent change in sAPP levels in AD, these CSF biomarkers may be valuable tools in treatment trials to monitor an effect on APP processing.…”

Comparison of Immunosorbent Assays for the Quantification of Biomarkers for Alzheimer’s Disease in Human Cerebrospinal Fluid

“…A substantial problem in the early diagnosis of AD is that clinical symptoms as measured by neuropsychological tests appear only after massive cell loss is already present in the brain. The clinical diagnosis of AD today is mainly based on the results of different neuropsychometric tests [1], laboratory tests [2,3], the patient’s history and clinical examinations. Recently, also brain imaging is emerging as a new tool in the diagnosis of AD [4,5].…”