Autoantibodies in Alzheimer's disease: potential biomarkers, pathogenic roles, and therapeutic implications

Wu, Jianming; L, Li

doi:10.7555/jbr.30.20150131

Cited by 74 publications

(27 citation statements)

References 108 publications

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“…An autoantibody screening study identified autoantibodies in CSF that target glia-derived nexin, actin-interacting proteins, metalloproteinase inhibitor 2, quinone oxidoreductase, inositol trisphosphate receptor 1, and endoplasmic reticulum calcium ATPase 2 [ 43 ]. The levels of autoantibodies targeting ATP synthase, angiotensin II type 1, and 5-hydroxytryptamine also are altered in AD [ 44 ]. The concentration of IgM and IgG autoantibodies targeting alpha B-crystallin is increased in AD patients [ 45 ].…”

Section: Role Of Igs In Admentioning

confidence: 99%

“…As the number of people developing AD is expected to increase, we need to develop low-cost and patient-friendly diagnostic techniques based on blood biomarkers. Autoantibodies are one candidate blood biomarker; indeed, anti-Aβ and -tau protein antibodies have been used as biomarkers [ 44 ]. Autoantibodies targeting Aβ have been studied by many groups.…”

Section: Role Of Igs In Admentioning

confidence: 99%

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The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease

Sim

Park

2020

IJMS

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Natural autoantibodies, immunoglobulins (Igs) that target self-proteins, are common in the plasma of healthy individuals; some of the autoantibodies play pathogenic roles in systemic or tissue-specific autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Recently, the field of autoantibody-associated diseases has expanded to encompass neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), with related studies examining the functions of Igs in the central nervous system (CNS). Recent evidence suggests that Igs have various effects in the CNS; these effects are associated with the prevention of neurodegeneration, as well as induction. Here, we summarize the functional roles of Igs with respect to neurodegenerative disease (AD and PD), focusing on the target antigens and effector cell types. In addition, we review the current knowledge about the roles of these antibodies as diagnostic markers and immunotherapies.

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Section: Role Of Igs In Admentioning

confidence: 99%

Section: Role Of Igs In Admentioning

confidence: 99%

The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease

Sim

Park

2020

IJMS

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“…Various novel blood- and CSF-based biomarkers for AD have been proposed in recent years. These include (1) neuroinflammatory markers such as reactive oxygen species (ROS), cytokines, chemokines, astrocytes, and activated microglia; (2) proinflammatory molecules such as interleukins (ILs), interferons (IFNs), and tumour necrosis factors (TNFs); (3) autoantibodies; (4) trace elements such as copper, zinc, iron; (5) fatty acids, sphingolipids, ceramides; (6) micro-RNAs; (7) circulating nanocomponents; and others [ 26 , 27 , 28 , 29 , 30 , 31 ]. Alternatively, non-invasive neuroimaging techniques such as computerized tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) offer structural and functional information about the brain, which may be able to support a diagnosis of dementia, but only in the later stages when brain shrinkage is evident.…”

Section: Introductionmentioning

confidence: 99%

Olfactory Dysfunction as a Global Biomarker for Sniffing out Alzheimer’s Disease: A Meta-Analysis

et al. 2018

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Cases of Alzheimer’s disease (AD) are rising exponentially due to increasing global life expectancy. There are approximately 50 million sufferers worldwide, with prevalence rising most rapidly in low-income countries such as Africa and Asia. There is currently no definite diagnosis of AD until after death, thus an early biomarker for AD is urgently required in order to administer timelier and more effective interventions. Olfactory dysfunction (problems with the sense of smell) is one of the earliest, preclinical symptoms observed in AD. Olfaction is a promising early biomarker for use worldwide as it is easy, cheap to measure, and not reliant on specialist clinicians or laboratory analysis. We carried out a meta-analysis to determine the credibility of olfaction in diagnosing AD in the preclinical stages, by comparing olfaction in healthy controls against AD patients and patients with mild cognitive impairment (MCI). Data from 10 articles were subjected to two comparative meta-analyses. In the case of AD, the results illustrated that the overall magnitude of effect size was more apparent, d = −1.63, 95% CI [−1.95, −1.31], in comparison to that of MCI, d = −0.81, 95% CI [−1.08, −0.55]. This shows that olfaction worsens progressively as patients progress from MCI to AD, highlighting the potential for olfactory dysfunction to identify AD in the preclinical stages prior to MCI.

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“…A distinct proportion of patients with dementia are immunotherapy-responsive [ 16 ], which indicates a dementia-related autoimmune background. Target-destructing autoantibodies, many of which are documented in [ 1 , 2 ], were preferentially discussed in this context. However, there is a new class of functional autoantibodies which bind to GPCRs.…”

Section: Discussionmentioning

confidence: 99%

“…Dementia in general and particularly Alzheimer’s disease are seen increasingly in association with an autoimmune background that could be causatively or supportively involved in the pathogenesis. In addition to the variety of autoantibodies (AABs) detected in patients with dementia and suggested to be pathogenic players, biomarkers and treatment targets such as those summarized in [ 1 , 2 ], there is a new class of autoantibodies, the so-called functional autoantibodies that are directed against G-protein coupled receptors (GPCRs; GPCR-AABs) which are increasingly seen as pathogenic players. For GPCR-AABs and the related diseases, which can be named “functional autoantibody disease”, basics, diagnostics and treatment strategies are summarized in [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Functional autoantibodies in patients with different forms of dementia

Wallukat¹,

Prüß²,

Müller³

et al. 2018

PLoS ONE

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Dementia in general and Alzheimer’s disease in particular is increasingly seen in association with autoimmunity being causatively or supportively involved in the pathogenesis. Besides classic autoantibodies (AABs) present in dementia patients, there is the new autoantibody class called functional autoantibodies, which is directed against G-protein coupled receptors (GPCRs; GPCR-AABs) and are seen as pathogenic players. However, less is known about dementia patients’ burden with functional autoantibodies. We present here for the first time a study analyzing the prevalence of GPCR-AABs in patients with different dementia forms such as unclassified, Lewy body, vascular and Alzheimer’s dementia. We identified the GPCR-AABs’ specific targets on the receptors and introduced a neutralization strategy for GPCR-AABs. Patients with Alzheimer’s and vascular dementia carried GPCR-AABs targeting the first loop of the alpha1- and the second loop of the beta2-adrenergic receptors (α1-AABs; β2-AABs). Nearly all vascular dementia patients also carry autoantibodies targeting the endothelin A receptor (ETA-AABs). The majority of patients with Lewy body dementia lacked any of the GPCR-AABs. In vitro, the function of the dementia-associated GPCR-AABs could be neutralized by the aptamer BC007. Due to the presence of GPCR-AABs in dementia patients mainly in those suffering from Alzheimer’s and vascular dementia, the orchestra of immune players in these dementia forms, so far preferentially represented by the classic autoantibodies, should be supplemented by functional autoantibodies. As dementia-associated functional autoantibodies could be neutralized by the aptamer BC007, the first step was taken for a new in vivo treatment option in dementia patients who were positive for GPCR-AABs.

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Autoantibodies in Alzheimer's disease: potential biomarkers, pathogenic roles, and therapeutic implications

Cited by 74 publications

References 108 publications

The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease

The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease

Olfactory Dysfunction as a Global Biomarker for Sniffing out Alzheimer’s Disease: A Meta-Analysis

Functional autoantibodies in patients with different forms of dementia

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