Serum Amyloid P‐Component and C‐Reactive Protein in Serum of Healthy Icelanders and Members of an Icelandic Family with Macroglobulinaemia

Jensson, O; Og, Björnsson; Árnason, Arnar; Birgisdóttir, Bryndís Eva; Pepys, MB

doi:10.1111/j.0954-6820.1982.tb01959.x

Cited by 15 publications

(3 citation statements)

References 13 publications

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“…Population-based cross-sectional surveys dealing with clinical correlations of CRP are few, not to mention longitudinal studies. Thus, it is not known to what extent a persistently raised CRP level can be a sign of an occult disease (8).…”

Section: Discussionmentioning

confidence: 99%

C‐reactive Protein in Population Samples

Palosuo

Husman

Koistinen

et al. 1986

Journal of Internal Medicine

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The significance of C‐reactive protein (CRP) was studied in three different sets of specimens. (a) Raised levels (>10 mg/1) were detected in 2.0% of 380 healthy blood donors from whom two blood specimens, taken at an interval of half a year, were tested. Except for two cases, only one of the two specimens was positive, (b) Raised levels were found three times as frequently (in 6.6%) in a random middle‐aged population sample consisting of 531 subjects. More than 40% of the raised levels could be connected to acute respiratory infections, and about 20% to smoking. Five of the 35 subjects (14%) in the population sample with elevated CRP had rheumatoid arthritis, (c) The third set of sera comprised pre‐illness specimens from 22 subjects who developed rheumatoid arthritis a few months to five years later. Although it had previously been proved that the majority of these sera contained rheumatoid factors, the CRP concentration was increased in one specimen only.

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Section: Discussionmentioning

confidence: 99%

C‐reactive Protein in Population Samples

Palosuo

Husman

Koistinen

et al. 1986

Journal of Internal Medicine

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“…Human SAP is not an acute phase reactant although in chronic inflammatory conditions, in which there is sustained increased production of CRP, SAP values tend to be slightly higher, albeit within the reference range 21 . A few small studies in the elderly and subjects with impaired cognition have reported plasma and CSF SAP concentrations above the reference range of the healthy middle aged population 2,22,23,24 . Children under 10 years have circulating SAP concentrations below the adult range but reduced adult SAP values are seen only with severe hepatocellular impairment 21 .…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

Genetic evidence for serum amyloid P component as a drug target for treatment of neurodegenerative disorders

Schmidt,

Finan,

Chopade

et al. 2023

Preprint

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The direct causes of neurodegeneration underlying Alzheimer's disease (AD) and many other dementias, are not known. Here we identify serum amyloid P component (SAP), a constitutive plasma protein normally excluded from the brain, as a potential drug target. After meta-analysis of three genome-wide association studies, comprising 44,288 participants, cis-Mendelian randomization showed that genes responsible for higher plasma SAP values are significantly associated with AD, Lewy body dementia and plasma tau concentration. These genetic findings are consistent with experimental evidence of SAP neurotoxicity and the strong, independent association of neocortex SAP content with dementia at death. Depletion of SAP from the blood and from the brain, as is provided by the safe, well tolerated, experimental drug, miridesap, may therefore contribute to treatment of neurodegeneration.

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“…Human SAP is not an acute phase reactant although in chronic inflammatory conditions, in which there is sustained increased production of CRP, SAP values tend to be slightly higher, albeit within the reference range [ 21 ]. A few small studies in the elderly and subjects with impaired cognition have reported plasma and CSF SAP concentrations above the reference range of the healthy middle-aged population [ 2 , 22 – 24 ]. Children under 10 years have circulating SAP concentrations below the adult range but reduced adult SAP values are seen only with severe hepatocellular impairment [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders

Schmidt,

Finan,

Chopade

et al. 2024

Open Biol.

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The mechanisms responsible for neuronal death causing cognitive loss in Alzheimer's disease (AD) and many other dementias are not known. Serum amyloid P component (SAP) is a constitutive plasma protein, which is cytotoxic for cerebral neurones and also promotes formation and persistence of cerebral A β amyloid and neurofibrillary tangles. Circulating SAP, which is produced exclusively by the liver, is normally almost completely excluded from the brain. Conditions increasing brain exposure to SAP increase dementia risk, consistent with a causative role in neurodegeneration. Furthermore, neocortex content of SAP is strongly and independently associated with dementia at death. Here, seeking genomic evidence for a causal link of SAP with neurodegeneration, we meta-analysed three genome-wide association studies of 44 288 participants, then conducted cis -Mendelian randomization assessment of associations with neurodegenerative diseases. Higher genetically instrumented plasma SAP concentrations were associated with AD (odds ratio 1.07, 95% confidence interval (CI) 1.02; 1.11, p = 1.8 × 10 −3 ), Lewy body dementia (odds ratio 1.37, 95%CI 1.19; 1.59, p = 1.5 × 10 −5 ) and plasma tau concentration (0.06 log 2 (ng l −1 ) 95%CI 0.03; 0.08, p = 4.55 × 10 −6 ). These genetic findings are consistent with neuropathogenicity of SAP. Depletion of SAP from the blood and the brain, by the safe, well tolerated, experimental drug miridesap may thus be neuroprotective.

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Serum Amyloid P‐Component and C‐Reactive Protein in Serum of Healthy Icelanders and Members of an Icelandic Family with Macroglobulinaemia

Cited by 15 publications

References 13 publications

C‐reactive Protein in Population Samples

C‐reactive Protein in Population Samples

Genetic evidence for serum amyloid P component as a drug target for treatment of neurodegenerative disorders

Genetic evidence for serum amyloid P component as a drug target in neurodegenerative disorders

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