Decrease of amyloid β1–42 antibodies in serum of patients with Alzheimer's disease

Brettschneider, S.; Morgenthaler, Nils G.; Teipel, SJ; Fischer-Schulz, Christina; Bürger, Katharina; Möller, H.-J.; Bergmann, Andreas; Hampel, Harald

doi:10.1055/s-2003-825282

Cited by 1 publication

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“…Similarly, naturally occurring autoantibodies to Aβ (NAb-Aβ) have been documented in human blood and CSF. 82,83 NAb reactivity was found to be increased for oligomeric assemblies as well as pyroglutamate modified Aβ, and these specific classes of IgGs declined with aging and advancing AD. 84 Moreover, higher levels of NAb to the Aβ Nterminus and lower NAb levels to Aβ mid-domain were found to correlate better with the cognitive decline.…”

Section: ■ Discussionmentioning

confidence: 96%

Citrullination of Amyloid-β Peptides in Alzheimer’s Disease

Mukherjee

Perez

Dubois

et al. 2021

ACS Chem. Neurosci.

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Protein citrullination (deimination of arginine residue) is a well-known biomarker of inflammation. Elevated protein citrullination has been shown to colocalize with extracellular amyloid plaques in postmortem AD patient brains. Amyloid-β (Aβ) peptides which aggregate and accumulate in the plaques of Alzheimer's disease (AD) have sequential Nterminal truncations and multiple post-translational modifications (PTM) such as isomerization, pyroglutamate formation, phosphorylation, nitration, and dityrosine cross-linking. However, no conclusive biochemical evidence exists whether citrullinated Aβ is present in AD brains. In this study, using high-resolution mass spectrometry, we have identified citrullination of Aβ in sporadic and familial AD brains by characterizing the tandem mass spectra of endogenous N-truncated citrullinated Aβ peptides. Our quantitative estimations demonstrate that ∼ 35% of pyroglutamate3-Aβ pool was citrullinated in plaques in the sporadic AD temporal cortex and ∼ 22% in the detergent-insoluble frontal cortex fractions. Similarly, hypercitrullinated pyroglutamate3-Aβ (∼ 30%) was observed in both the detergent-soluble as well as insoluble Aβ pool in familial AD cases. Our results indicate that a common mechanism for citrullination of Aβ exists in both the sporadic and familial AD. We establish that citrullination of Aβ is a remarkably common PTM, closely associated with pyroglutamate3-Aβ formation and its accumulation in AD. This may have implications for Aβ toxicity, autoantigenicity of Aβ, and may be relevant for the design of diagnostic assays and therapeutic targeting.

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Section: ■ Discussionmentioning

confidence: 96%