The Diagnostic Value of CSF Amyloid-β₄₃ in Differentiation of Dementia Syndromes

Abstract

Amyloid-β (Aβ) is known as the most prominent core protein in Alzheimer's Disease (AD) senile plaques. Although research has focused mainly on Aβ40 and Aβ42 as potential cerebrospinal fluid (CSF) biomarkers, a range of Aβ peptides with variable lengths has been demonstrated in the brains and CSF of AD patients. Recently, it has been found that the Aβ43 peptide may be more abundant than previously assumed, could therefore play an important role in AD pathophysiology, and hence also function as putative biomarker. In this study the value of CSF Aβ43 in AD diagnosis was investigated. Aβ43 levels in CSF were highly correlated with Aβ42 levels. Furthermore, in differentiation of AD from nondemented controls and from patients with Lewy body dementia and frontotemporal dementia, Aβ43 had an equal diagnostic value as Aβ42, both as a single biomarker and in combination with total and phosphorylated tau. In conclusion, quantification of Aβ43 in CSF does not add novel diagnostic information to the differential diagnosis of AD compared to existing biomarkers.

Cerebrospinal Fluid Levels of Amyloid Beta 1–43 in Patients with Amnestic Mild Cognitive Impairment or Early Alzheimer’s Disease: A 2-Year Follow-Up Study

“…This is a small study with groups of limited size. In an earlier study of similar size that compared AD patients with controls, CSF Aβ43 was found to have similar specificity (97%) but much lower sensitivity (52%) and lower AUC (0.77) than in the current study ( Bruggink et al, 2013 ). Such differences between studies arise easily when comparing small groups, and the present data should therefore be confirmed in a larger material.…”

“…It has been demonstrated that CSF Aβ43 was decreased in MCI and AD patients, as well as being positively correlated to CSF Aβ42 ( Kakuda et al, 2012 ), despite Aβ43 and Aβ42 being produced by different enzymic routes ( Qi-Takahara et al, 2005 ). CSF Aβ43 was found to be slightly inferior to Aβ42 for separating controls from AD patients ( Bruggink et al, 2013 ).…”

Cerebrospinal Fluid Aβ43 Is Reduced in Early-Onset Compared to Late-Onset Alzheimer’s Disease, But Has Similar Diagnostic Accuracy to Aβ42

“…Moreover, knock-in mice bearing the pathogenic presenilin-1 R278I mutation demonstrated overproduction of Aβ43, impaired short-term memory and acceleration of amyloid-β pathology (Saito et al, 2011). Aβ43 correlates positively with age in patients with AD (Bruggink et al, 2013), and correlates closely with CSF Aβ42 both in patients and control individuals (Bruggink et al, 2013; Lauridsen et al, 2016). As far as we know, no study as yet has compared CSF levels of Aβ43 in early-onset AD with late-onset AD.…”

Current state of Alzheimer’s fluid biomarkers

“…Several subsequent studies have consistently shown that CSF levels of Aβ42 correlate inversely with plaque load as observed in autopsies and in vivo with positron emission tomography (PET) [ 82 , 114 , 158 , 343 , 353 ]. CSF Aβ43 is also reported to decrease in AD, but it has similar diagnostic accuracy to CSF Aβ42 [ 39 , 193 ] so research has focused on the latter.…”