Increased tissue factor pathway inhibitor and homocysteine in Alzheimer's disease

Piazza, Fabrizio; Galimberti, Gloria; Conti, Elisa; Isella, Valeria; Perlangeli, Maria V.; Speranza, Tiziana; Borroni, Barbara; Pogliani, Enrico Maria; Padovani, Alessandro; Ferrarese, Carlo

doi:10.1016/j.neurobiolaging.2010.02.016

Cited by 23 publications

(24 citation statements)

References 41 publications

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“…One of the most valuable hypotheses explaining the mechanisms by which homocysteine contributes to AD pathology is by affecting the cerebrovascular and endothelial compartments, resulting in a chronic perturbation of the neurovascular unit. A direct link between hyperhomocysteinemia and both an increase of endothelial damage and prothrombotic state in AD has been recently demonstrated by Piazza et al 24 Raposo et al also indicate that both compounds, homocysteine and thiolactone, inhibit the activity of lysyl oxidase (an enzyme involved in extracellular matrix maturation) in vascular endothelial cells. 25 Several lines of evidence suggest that chronic endothelial dysfunction plays a pivotal role in AD.…”

Section: Discussionmentioning

confidence: 89%

Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer’s disease

Kim¹,

Lee²

2014

NDT

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PurposeHomocysteine has been associated with cognitive impairment and various psychiatric symptoms. This study was designed to clarify whether a relationship exists between the serum levels of homocysteine and the behavioral and psychological symptoms of dementia.MethodsPatients with Alzheimer’s disease (n=77) and control subjects (n=37) were included in this study. History taking, physical examination, and cognitive assessment were carried out as part of the investigation for the diagnosis of Alzheimer’s disease based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Mini-Mental State Examination, Global Deterioration Scale, Clinical Dementia Rating, and the Korean version of the Neuropsychiatric Inventory were applied to all patients. The patients’ serum homocysteine, folate, and vitamin B12 levels were measured.ResultsPatients with Alzheimer’s disease had statistically significantly lower Mini-Mental State Examination scores and higher serum homocysteine levels compared to the control subjects. Mean serum folate and vitamin B12 concentration were significantly lower in patients with Alzheimer’s disease compared to control subjects. A statistically significant positive correlation was found between the serum homocysteine levels and the Neuropsychiatric Inventory subdomains, including delusion, agitation/aggression, depression/dysphoria, elation/euphoria, apathy/indifference, and disinhibition. No statistically significant correlation was found between the serum homocysteine concentration and the Mini-Mental State Examination, Global Deterioration Scale, or Clinical Dementia Rating.ConclusionAssociations between the serum homocysteine levels and behavioral and psychological symptoms of dementia were observed, raising the possibility of an etiological role. However, the correlations between the folate or vitamin B12 levels and the Neuropsychiatric Inventory scores were not significant. The pathophysiological mechanisms underlying these findings remain to be elucidated. This was a cross-sectional study and the findings should be confirmed by repetitive, prospective longitudinal studies in a larger group of patients with neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 89%

Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer’s disease

Kim¹,

Lee²

2014

NDT

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“…A similar hypothesis has already been proposed for AD, in which vascular damage induced by Ab was suggested to be a key step in the pathogenesis of the disease. [21][22][23][24] Studies aimed at quantifying the amount of naturally occurring anti-Ab antibodies have so far shown scanty and conflicting results. Anti-Ab autoantibodies levels in AD patients were found to be reduced by some authors, [25][26][27] partially modified 28 or unchanged by others, 29,30 and even increased in further studies.…”

Section: Discussionmentioning

confidence: 99%

Anti–amyloid β autoantibodies in cerebral amyloid angiopathy–related inflammation: Implications for amyloid‐modifying therapies

Piazza

Greenberg

Savoiardo

et al. 2013

Annals of Neurology

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Our data support the hypothesis that the pathogenesis of CAA-ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti-Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA-ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti-Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid-modifying therapies for the treatment of AD and CAA.

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“…Importantly, three positive candidates from this study are associated with neurodegenerative disease in patients: C01A2.4/CHMP2B [frontotemporal dementia and degeneration; (Isaacs et al, 2011)]; gpd-2 /GAPDH [Parkinson’s, Alzheimer’s, and Huntington’s (Mazzola and Sirover, 2001)]; and C54D10.10/TFPI [Alzheimer’s (Piazza et al, 2012)]. Notably, we did not identify C. elegans orthologs of other known heritable PD genes among these modifiers.…”

Section: Discussionmentioning

confidence: 99%

The Glycolytic Enzyme, GPI, Is a Functionally Conserved Modifier of Dopaminergic Neurodegeneration in Parkinson’s Models

et al. 2014

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SUMMARY Neurodegenerative diseases represent an increasing burden in our aging society, yet the underlying metabolic factors influencing onset and progression remain poorly defined. The relationship between impaired IGF-1/insulin-like signaling (IIS) and lifespan extension represents an opportunity to investigate the interface of metabolism with age-associated neurodegeneration. Using datasets of established daf-2/IIS-signaling components in Caenorhabditis elegans, we conducted systematic RNAi screens in worms to select for daf-2-assoicated genetic modifiers of α-synuclein misfolding and dopaminergic neurodegeneration, two clinical hallmarks of Parkinson’s disease. An outcome of this strategy was the identification of gpi-1/GPI, an enzyme in glucose metabolism, as a daf-2-regulated modifier that acts independent of the downstream cytoprotective transcription factor, DAF-16/FOXO, to modulate neuroprotection. Subsequent mechanistic analyses using Drosophila and mouse primary neuron cultures further validated the conserved nature of GPI neuroprotection from α-synuclein proteotoxicity. Collectively, these results support glucose metabolism as a conserved functional node at the intersection of proteostasis and neurodegeneration.

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Increased tissue factor pathway inhibitor and homocysteine in Alzheimer's disease

Cited by 23 publications

References 41 publications

Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer’s disease

Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer’s disease

Anti–amyloid β autoantibodies in cerebral amyloid angiopathy–related inflammation: Implications for amyloid‐modifying therapies

The Glycolytic Enzyme, GPI, Is a Functionally Conserved Modifier of Dopaminergic Neurodegeneration in Parkinson’s Models

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Increased tissue factor pathway inhibitor and homocysteine in Alzheimer's disease

Cited by 23 publications

References 41 publications

Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer&rsquo;s disease

Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer&rsquo;s disease

Anti–amyloid β autoantibodies in cerebral amyloid angiopathy–related inflammation: Implications for amyloid‐modifying therapies

The Glycolytic Enzyme, GPI, Is a Functionally Conserved Modifier of Dopaminergic Neurodegeneration in Parkinson’s Models

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Product

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Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer’s disease

Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer’s disease