Preferential association of serum amyloid P component with fibrillar deposits in familial British and Danish dementias: Similarities with Alzheimer's disease

Rostagno, Agueda; Lashley, Tammaryn; Ng, Douglas; Meyerson, Jordana L; Brændgaard, Hans; Plant, Gordon T.; Bojsen‐Møller, Marie; Holton, Janice L.; Frangione, Blas; Révész, Tamás; Ghiso, Jorge

doi:10.1016/j.jns.2007.01.050

Cited by 23 publications

(11 citation statements)

References 60 publications

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“…Further in vitro studies indicated that a certain degree of A aggregation is required for C1q binding and the initiation of C activation [97,99,143,146]. The binding of C1q to A was initially proposed to occur through its collagen tail [98], similar to C1q-SAP, C1q-DNA and C1q-C-reactive protein (CRP) interactions [102,147].…”

Section: Binding Of C1 To a Results In C Activation And C3b Binding Tmentioning

confidence: 99%

Histological and Direct Evidence for the Role of Complement in the Neuroinflammation of AD

Veerhuis

2011

CAR

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In Alzheimers's disease (AD) a disturbed balance between synthesis and removal of Aβ leads to the formation of Aβ deposits and a reaction of the innate immune system. Little evidence exists for a contribution of the adaptive immune response in AD, as no signs of influx of blood borne cells or presence of immunoglobulins in Aβ deposits are apparent. Factors of the complement(C) system and pentraxins act as pattern recognition molecules and mediate uptake of Aβ by glial cells expressing C-receptors (Crec). These interactions may, however, also lead to synthesis and secretion of reactive oxygen species (ROS), cytokines, chemokines and other potentially neurotoxic agents by the glial cells. Virtually all complement factors are produced in brain, and the expression is increased in AD affected brain areas. In AD brain areas with amyloid deposits especially classical pathway C activation products are readily observed. Also C regulatory proteins (Creg) and Crec can be found in the brain parenchyma and are upregulated, especially under acute inflammatory conditions, such as meningitis. However, under chronic low-grade inflammatory conditions, such as in AD, Creg and to some extent Crec expression may remain at a low level, thereby allowing C activation to proceed, leading to sustained activation of glial cells and neurodegenerative changes. In this review evidence from immunohistochemical, in vitro and animal studies pointing to a role for C activation is discussed, with special focus on the disturbed balance between C activators and Cregs in AD.

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Section: Binding Of C1 To a Results In C Activation And C3b Binding Tmentioning

confidence: 99%

Histological and Direct Evidence for the Role of Complement in the Neuroinflammation of AD

Veerhuis

2011

CAR

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“…Much remains to be discovered, ensuring that exciting times lie ahead. , α2M (Fabrizi et al, 2001), Hp (Powers et al, 1981), SAP (Perlmutter et al, 1995) Spongiform encephalopathies Prion Protein Extracellular Clus (Chiesa et al, 1996;Freixes et al, 2004), α2M (Adler and Kryukov 2007), SAP (Ishii et al, 1984) Parkinson's disease α-synuclein Intracellular Clus , SAP (Kalaria and Grahovac 1990), α2M (Nicoletti et al, 2002) Dementia with lewy bodies α-synuclein Intracellular Clus , SAP (Kalaria and Grahovac 1990) , SAP (Rostagno et al, 2007) Familial Danish Dementia ADan Extracellular Clus (Lashley et al, 2006), SAP (Rostagno et al, 2007) Familial amyloid polyneuropathy TTR Extracellular Unknown…”

Section: Discussionmentioning

confidence: 99%

Extracellular Chaperones and Amyloids

Wilson¹,

Yerbury²,

Poon³

2008

Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection

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The pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. In this scenario, EC receptors are a critical part of a quality control system which protects the brain against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacerabate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies. ABSTRACTThe pathology of more than 40 human degenerative diseases is associated with fibrillar proteinaceous deposits called amyloid. Collectively referred to as protein deposition diseases, many of these affect the brain and the central nervous system. In many cases the amyloid deposits are extracellular and are found associated with newly identified abundant extracellular chaperones (ECs). Evidence is discussed which suggests an important regulatory role for ECs in amyloid formation and disposal in vivo. This is emerging as an exciting field. A model is presented in which it is proposed that, under normal conditions, ECs stabilize extracellular misfolded proteins by binding to them, and then guide them to specific receptors for uptake and subsequent degradation. In this scenario, EC receptors are a critical part of a quality control system which protects the brain against dangerously hydrophobic proteins/peptides. However, it also appears possible that in the presence of a high molar excess of misfolded protein, such as might occur during disease, the limited amounts of ECs available may actually exacebate pathology. Further advances in understanding of the mechanisms that control extracellular protein folding are likely to identify new strategies for effective disease therapies.

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“…SAP binding to its ligands can, in turn, lead to binding of complement factor C1q and initiate activation of the classical pathway of the complement system. SAP binding to newly formed amyloid fibrils may protect the A ␤ deposits from proteolysis, and as a consequence promote A ␤ fibril and amyloid plaque formation in the brain [11,[13][14][15][16] . Clustering of activated microglial cells in A ␤ plaques was observed in SAP-and C1q-containing A ␤ plaques preceding tau-related neurodegenerative changes [17] .…”

Section: Introductionmentioning

confidence: 99%

Serum Amyloid P Component as a Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease

Verwey

Schuitemaker²,

Flier³

et al. 2008

Dement Geriatr Cogn Disord

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Background: Serum amyloid P component (SAP), present in amyloid-β (Aβ) plaques in Alzheimer’s disease (AD), may protect Aβ deposits against proteolysis, thereby promoting plaque formation. The aim was to investigate if SAP levels in cerebrospinal fluid (CSF) and serum can be used to discriminate controls, AD and mild cognitive impairment (MCI) patients, and to identify incipient AD among MCI patients. Methods: SAP levels in CSF and serum were determined in 30 controls, 67 MCI and 144 AD patients. At follow-up, 39 MCI patients had progressed to dementia, while 25 had remained stable (mean follow-up time: 2.6 ± 1.0 and 2.1 ± 0.8 years). Results: Cross-sectionally no differences were found in SAP levels in CSF and serum between the groups. MCI patients that had progressed to dementia at follow-up had lower CSF SAP levels (13 mg/l, range 3.3–199.3 mg/l) than MCI nonprogressors (20.2 mg/l, range 7.0–127.7 mg/l; p < 0.05). A low CSF SAP level was associated with a 2-fold increased risk of progression to AD (hazard ratio = 2.2; 95% confidence interval = 0.9–5.4). Conclusion: Our data suggest that measurement of CSF SAP levels can aid in the identification of incipient AD among MCI patients.

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Preferential association of serum amyloid P component with fibrillar deposits in familial British and Danish dementias: Similarities with Alzheimer's disease

Cited by 23 publications

References 60 publications

Histological and Direct Evidence for the Role of Complement in the Neuroinflammation of AD

Histological and Direct Evidence for the Role of Complement in the Neuroinflammation of AD

Extracellular Chaperones and Amyloids

Serum Amyloid P Component as a Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease

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