Fibrinogen and Altered Hemostasis in Alzheimer's Disease

Cortes‐Canteli, Marta; Zamolodchikov, Daria; Ahn, Hyung Jin; Strickland, Sidney; Norris, Erin H.

doi:10.3233/jad-2012-120820

Cited by 151 publications

(159 citation statements)

References 94 publications

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“…Fibrinogen-A␤ interactions have been shown to induce oligomerization of fibrinogen and fibrillation of the A␤ peptide (76). Abnormal depositions of fibrinogen have been found in AD patients.…”

Section: Serum Amyloid P Component and Fibrinogenmentioning

confidence: 99%

“…The levels of galectin-3, associated with idiopathic pulmonary fibrosis, are increased in the serum of AD patients. In vitro galectin-3 has been found to reduce the neurotoxicity of A␤42 (76). The levels of lactadherin, playing a vital role in phagocytosis, are decreased in AD patients (77).…”

Section: Other Amyloid Proteinsmentioning

confidence: 99%

“…TTR (59), CysC (67), and apoA-I (62) all suppress A␤ fibrillation and delay AD progression in mice (57,64). In contrast, ␣-syn (23), tau (28), and fibrinogen-␣ (95) promote A␤ toxicity and/or fibrillation and increase the risk of AD in mice (32) and/or patients (25,76). IAPP prevents A␤ fibrillation in vitro (50), yet IAPP-associated T2D may promote AD progression in vivo.…”

Section: Implications Of A␤ Cross-amyloid Interactionsmentioning

confidence: 99%

“…Abnormal depositions of fibrinogen have been found in AD patients. Similar to SAP, fibrinogen modulates A␤ deposition and fibrillation, and also further affects neurodegeneration (76).…”

Section: Serum Amyloid P Component and Fibrinogenmentioning

confidence: 99%

See 3 more Smart Citations

Cross-interactions between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis

Luo

Wärmländer

Gräslund

et al. 2016

Journal of Biological Chemistry

128

108

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Many protein folding diseases are intimately associated with accumulation of amyloid aggregates. The amyloid materials formed by different proteins/peptides share many structural similarities, despite sometimes large amino acid sequence differences. Some amyloid diseases constitute risk factors for others, and the progression of one amyloid disease may affect the progression of another. These connections are arguably related to amyloid aggregates of one protein being able to directly nucleate amyloid formation of another, different protein: the amyloid cross-interaction. Here, we discuss such cross-interactions between the Alzheimer disease amyloid-␤ (A␤) peptide and other amyloid proteins in the context of what is known from in vitro and in vivo experiments, and of what might be learned from clinical studies. The aim is to clarify potential molecular associations between different amyloid diseases. We argue that the amyloid cascade hypothesis in Alzheimer disease should be expanded to include cross-interactions between A␤ and other amyloid proteins.Alzheimer disease (AD) 3 is the most common form of elderly dementia. Its causes have not yet been clearly elucidated. The two classical AD lesions are depositions of intracellular neurofibrillary tau tangles and extracellular deposits of aggregated amyloid-␤ (A␤) peptides in amyloid plaques in the gray matter of the brain, mainly the hippocampus and neocortex. A␤ is a 36 -43-residue peptide cleaved from the amyloid-␤ protein precursor (A␤PP) by ␥-secretase and ␤-secretase enzymes.Some A␤PP and A␤ mutations increase A␤ production and deposition and/or extend the half-life of A␤ in the brain, but only a fraction (5%) of Alzheimer disease is familial AD (1). Several studies indicate that alterations of the pathologies of other amyloid proteins such as ␣-synuclein (2) and tau (3) are observed in familial AD.The amyloid cascade hypothesis suggests that deposition of A␤ aggregates in brain plays a vital role in AD development (4). The amyloid form of A␤ aggregates is generally defined by in vitro observations: originally by the so-called cross-␤ x-ray diffraction pattern or by observation of fibril structures in microscopy (transmission electron microscopy or atomic force microscopy) (5). Molecular probes recognizing the formation of certain ordered molecular structures include Congo red and thioflavin T, which change their optical properties when bound to amyloid material (5). The terms "on-pathway" and "off-pathway" intermediates are used to differentiate between self-aggregated A␤ species that lead to amyloid formation and those that do not. Missense mutations in the A␤PP, apoE, PS1, and PS2 genes can increase accumulation and toxicity of A␤ aggregates, and the "on-pathway" intermediate aggregates seem to be the most cell-damaging species (6). This provides strong support for the amyloid cascade hypothesis, which nevertheless remains disputed.Although two recent reviews (7, 8) respectively reject and support the amyloid cascade hypothesis, they both agree on one poin...

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Section: Serum Amyloid P Component and Fibrinogenmentioning

confidence: 99%

Section: Other Amyloid Proteinsmentioning

confidence: 99%

Section: Implications Of A␤ Cross-amyloid Interactionsmentioning

confidence: 99%

“…Abnormal depositions of fibrinogen have been found in AD patients. Similar to SAP, fibrinogen modulates A␤ deposition and fibrillation, and also further affects neurodegeneration (76).…”

Section: Serum Amyloid P Component and Fibrinogenmentioning

confidence: 99%

See 2 more Smart Citations

Cross-interactions between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis

Luo

Wärmländer

Gräslund

et al. 2016

Journal of Biological Chemistry

128

108

View full text Add to dashboard Cite

show abstract

“…However, immediately after HI IGF-1 gene expression is reduced [7], there is reduced expression of intracellular pathways activated by IGF-1 such as phosphorylated Akt [8]. Furthermore, the mRNA transcripts encoding IGF-1 receptors either remain the same or decrease after brain injury [6,9], and the IGFBPs show different temporal and spatial expression depending on the degree of injury. These data suggest that in some types of injury there may be insufficient endogenous IGF-1 to facilitate effective brain recovery [10].…”

Section: Endogenous Response Of Igf-1 To Brain Injurymentioning

confidence: 95%

The role for IGF-1-derived small neuropeptides as a therapeutic target for neurological disorders

Guan

Harris

Brimble

et al. 2015

Expert Opinion on Therapeutic Targets

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These small neuropeptides provide effective neuroprotection by offering an improved pharmacokinetic profile and more practical route of administration compared with IGF-1 administration. Developing modified neuropeptides to overcome the limitations of their endogenous counterparts represents a novel strategy of pharmaceutical discovery for neurological disorders. The mechanism of action may involve a regulation of IGF-1 bioavailability.

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Relationship Between Cyclophilin A Levels and Matrix Metalloproteinase 9 Activity in Cerebrospinal Fluid of Cognitively Normal Apolipoprotein E4 Carriers and Blood-Brain Barrier Breakdown

et al. 2013

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In humans, apolipoprotein E (apoE) has 3 isoforms: apoE2, apoE3, and apoE4. APOE4 is a major genetic risk factor for Alzheimer disease (AD). 1 Apolipoprotein E4 has direct effects on the cerebrovascular system, resulting in microvascular lesions and blood-brain barrier (BBB) damage, as recently reviewed. 2 Neurovascular dysfunction is also present in cognitively normal APOE4 carriers and individuals with APOE4-associated disorders including AD. 1-3 Moreover, postmortem brain tissue analysis has indicated that BBB breakdown in patients with AD is more pronounced in APOE4 carriers compared with APOE3 or APOE2. [4][5][6] Our recent studies in transgenic mice have demonstrated that apoE4 leads to BBB breakdown by activating the proinflammatory cyclophilin A (CypA)-matrix metalloproteinase 9 (MMP-9) pathway in brain pericytes, which in turn results in degradation of the BBB tight junctions and basement membrane proteins. 7 It has also been shown that apoE4-mediated BBB breakdown leads to secondary neuronal injury and cognitive decline in transgenic mice. 7 Apolipoprotein E2 and apoE3 maintained normal BBB integrity in transgenic mice by suppressing the CypA-MMP-9 pathway. 7 Here, we studied the cerebrospinal fluid (CSF)/plasma albumin quotient (Q Alb ), an established marker of BBB breakdown, 8 and CypA and active MMP-9 levels in the CSF of cognitively normal individuals with different APOE genotypes to determine whether apoE4dependent changes in BBB permeability and CypA-MMP-9 pathway as shown in APOE4, but not APOE3 and APOE2 transgenic mice, also occur in humans.

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Fibrinogen and Altered Hemostasis in Alzheimer's Disease

Cited by 151 publications

References 94 publications

Cross-interactions between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis

Cross-interactions between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis

The role for IGF-1-derived small neuropeptides as a therapeutic target for neurological disorders

Relationship Between Cyclophilin A Levels and Matrix Metalloproteinase 9 Activity in Cerebrospinal Fluid of Cognitively Normal Apolipoprotein E4 Carriers and Blood-Brain Barrier Breakdown

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