Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals

Weksler, Marc E.; Relkin, Norman; Turkenich, Rimma; LaRusse, Susan; Zhou, Ling; Szabo, Paul

doi:10.1016/s0531-5565(02)00029-3

Cited by 188 publications

(136 citation statements)

References 15 publications

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“…Some studies report decreased binding activity (5,50), and others, increased binding activity (6,51). The discrepancy may derive from the assay of free Ab concentrations in these studies (as opposed to total Ab concentrations that take into account the amount of Abs complexed to A␤).…”

Section: Discussionmentioning

confidence: 94%

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Autoantibody-catalyzed Hydrolysis of Amyloid β Peptide

Taguchi

Planque

Nishiyama

et al. 2008

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 94%

“…A␤ binding autoantibodies are present in healthy humans, AD patients (5,6), and pooled human IgG marketed as IVIG (intravenously administered immunoglobulins) formulations (7)). Phase 1 human clinical trials have suggested that infusion of pooled human IgG into the peripheral circulation may be useful in treating AD (7).…”

mentioning

confidence: 99%

Autoantibody-catalyzed Hydrolysis of Amyloid β Peptide

Taguchi

Planque

Nishiyama

et al. 2008

Journal of Biological Chemistry

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“…Furthermore, much evidences suggest the involvement of a systemic immune response in the pathogenesis of AD (Britschgi and Wyss-Coray, 2007;Speciale et al, 2007). Indeed, blood derived cells seem to accumulate in the AD brain (Rogers et al, 1998), while other studies have shown changes in the distribution and reactivity of immune cells in the blood Britschgi and Wyss-Coray, 2007;Monsonego et al, 2003;Weksler et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

Bulati¹,

Buffa²,

Candore³

et al. 2011

Ageing Research Reviews

101

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a b s t r a c tImmunosenescence contributes to the decreased ability of the elderly to control infectious diseases, which is also reflected in their generally poor response to new antigens and vaccination. It is known that the T cell branch of the immune system is impaired in the elderly mainly due to expansion of memory/effector cells that renders the immune system less able to respond to new antigens. B lymphocytes are also impaired in the elderly in terms of their response to new antigens. In this paper we review recent work on B cell immunosenescence focusing our attention on memory B cells and a subset of memory B cells (namely IgG + IgD − CD27 − ) that we have demonstrated is increased in healthy elderly.

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“…The titers of these antibodies are low, and their origin and physiological or pathological role is unknown. Using crude methods A␤ antibody titers were found to be increased (22), decreased (23,27,28), or unchanged (21) in AD compared with healthy controls, but a large-scale analysis of A␤ antibody subspecificities or changes in antibody repertoire with age or in response to A␤ vaccination has not been described. Based on the presence of A␤ antibodies in normal plasma and the promise of therapeutic A␤ vaccines polyclonal i.v.…”

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confidence: 99%

Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease

Britschgi¹,

Olin²,

Johns³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

173

163

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A number of distinct ␤-amyloid (A␤) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural A␤-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic A␤ and amyloidogenic non-A␤ species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of A␤ and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of A␤1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant A␤, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from A␤ toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with A␤ the monkeys developed high titers not only against A␤ peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of A␤ antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD. A lzheimer's disease (AD) is the most common cause of dementia, affecting an estimated 5.3 million individuals in the United States alone. Deposits of ␤-amyloid peptide (A␤) in extracellular plaques characterize the AD brain, but soluble oligomeric A␤ species appear to be more neurotoxic than plaques and interfere with synaptic function (reviewed in ref. 1). Notably, most A␤ peptides isolated from AD brains are posttranslationally modified and truncated (2-6), and some are proposed to be oxidized (7,8) or cross-linked at Tyr-10 (9). Although the pathogenic consequences of these modifications need to be resolved, most of them can stabilize A␤ assemblies, interfere with proteolytic degradation, and increase A␤ toxicity in vitro (7,8,10).One line of defense against toxic A␤ species could be neutralizing antibodies. Stimulating the production of A␤ antibodies by active immunization with synthetic A␤ (11) or administering monoclonal A␤ antibodies (12, 13) reduced amyloid pathology and inflammation and improved cognitive function in mouse models of AD (14). In patients with mild to moderate AD active immunization appears to reduce plaque load (15), and in some patients production of A␤ antibodies correlated with attenuated cognitive decline (16). It has also been suggested that antibodies recognizing different domains (12,13,17) or conformations (18, 19) of A␤ may have different efficacy in humans.Interestingly, antibodies agai...

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Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals

Cited by 188 publications

References 15 publications

Autoantibody-catalyzed Hydrolysis of Amyloid β Peptide

Autoantibody-catalyzed Hydrolysis of Amyloid β Peptide

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease

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