Beta-amyloid auto-antibodies are reduced in Alzheimer's disease

Qu, Bao-Xi; Gong, Yunhua; Moore, Carol; Fu, Min; German, Dwight C.; Chang, Ling Yu; Rosenberg, Roger N.

doi:10.1016/j.jneuroim.2014.06.017

Cited by 44 publications

(36 citation statements)

References 42 publications

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“…The nAbs-Aβ-ELISA showed a high interassay variability. Aggregation of Aβ during the coating process is a possible explanation for this effect [45]. In contrast to our assay design, many ELISAs that investigate nAbs-Aβ antibody titers and that have been reported by others were not controlled for typical quality criteria like unspecific background, interassay variability, or limit of detection and thus their assay performance remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Naturally Occurring Autoantibodies against Tau Protein Are Reduced in Parkinson's Disease Dementia

et al. 2016

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Background and ObjectiveAltered levels of naturally occurring autoantibodies (nAbs) against disease-associated neuronal proteins have been reported for neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). Recent histopathologic studies suggest a contribution of both Lewy body- and AD-related pathology to Parkinson's disease dementia (PDD). Therefore, we explored nAbs against alpha-synuclein (αS), tau and β-amyloid (Aβ) in PDD compared to cognitively normal PD patients.Materials and MethodsWe established three different ELISAs to quantify the nAbs-tau, nAbs-αS, and nAbs-Aβ levels and avidity towards their specific antigen in serum samples of 18 non-demented (PDND) and 18 demented PD patients (PDD), which were taken from an ongoing multi-center cohort study (DEMPARK/LANDSCAPE).ResultsPDD patients had significantly decreased nAbs-tau serum levels compared to PDND patients (p = 0.007), whereas the serum titers of nAbs-αS and nAbs-Aβ were unchanged. For all three nAbs, no significant differences in avidity were found between PDD and PDND cohorts. However, within both patient groups, nAbs-tau showed lowest avidity to their antigen, followed by nAbs-αS, and nAbs-Aβ. Though, due to a high interassay coefficient of variability and the exclusion of many samples below the limit of detection, conclusions for nAbs-Aβ are only conditionally possible.ConclusionWe detected a significantly decreased nAbs-tau serum level in PDD patients, indicating a potential linkage between nAbs-tau serum titer and cognitive deficits in PD. Thus, further investigation in larger samples is justified to confirm our findings.

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Section: Discussionmentioning

confidence: 99%

Naturally Occurring Autoantibodies against Tau Protein Are Reduced in Parkinson's Disease Dementia

et al. 2016

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“…It seems that different APOE alleles are not associated with an increase in Aβ production, but with an inability to clear Aβ from the brain (Mawuenyega et al, 2010; Castellano et al, 2011). This may be related to the reduced production of Aβ auto-antibodies in AD subjects (Qu et al, 2014). …”

Section: Clinical and Neuropathological Criteria For Ad Diagnosismentioning

confidence: 99%

Monoaminergic neuropathology in Alzheimer’s disease

Šimić

Leko

Wray³

et al. 2017

Progress in Neurobiology

241

142

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None of the proposed mechanisms of Alzheimer’s disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5–20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid β as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD.

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“…Previous studies indicated that Aβ species could initiate antibody production in vivo. 7,25 Importantly, microglia activation depends on Aβ conformation and core fragment/epitope of Aβ is related to neuroinflammation. 26 We speculated that editing the hydrophobicity of epitope Aβ17-24 with CRANAD-17 could change immuneresponses of Aβ and consequently alter pro-inflammatory properties of Aβ.…”

Section: Resultsmentioning

confidence: 99%

A screening platform based on epitope editing for drug discovery

Zhu

Yang

Van

et al. 2019

Preprint

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The interaction between an antibody and its epitope has been daily utilized in various biological studies; however it has been rarely explored whether small molecules can alter the interaction. We discovered that small molecules could alter/edit surface properties of amyloid beta (Aβ) epitopes, and consequently inhibit or enhance corresponding antibody recognition. Remarkably, this editing effect could generate functional changes including protein aggregation behaviors, cell cytokine secreting and in vivo microglia activation. According to this discovery, we proposed a screen 2 platform based on epitope editing for drug discovery (SPEED). With a small library of compounds, we validated that SPEED could be used to seek new leads for Aβ species.We also demonstrated that this platform could potentially be extended to other targets including tau protein and PD-L1 protein. The SPEED is a simple, fast and label-free screening method. We believe that the SPEED strategy could be universally applicable for seeking and validating drug candidates and imaging ligands.

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Beta-amyloid auto-antibodies are reduced in Alzheimer's disease

Cited by 44 publications

References 42 publications

Naturally Occurring Autoantibodies against Tau Protein Are Reduced in Parkinson's Disease Dementia

Naturally Occurring Autoantibodies against Tau Protein Are Reduced in Parkinson's Disease Dementia

Monoaminergic neuropathology in Alzheimer’s disease

A screening platform based on epitope editing for drug discovery

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