P4–023: Cerebrospinal fluid of Alzheimer patients promotes beta–amyloid fibril formation in vitro

Ono, Kenjiro; Noguchi, Moeko; Matsumoto, Y.; Yanase, Daisuke; Iwasa, Kazuo; Naiki, H.; Yamada, Masahito

doi:10.1016/j.jalz.2006.05.1761

Cited by 5 publications

(7 citation statements)

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“…Elevation of endogenous formaldehyde levels may be related to the pathogenic process in neurodegenerative diseases [73][74][75]. In one such example, namely age-related cognitive impairment, an increase in extracellular formaldehyde level was observed in the cerebrospinal fluid [76,77]. AD is characterized by loss of neurons and synapses in the cerebral cortex and certain subcortical regions.…”

Section: Discussionmentioning

confidence: 99%

Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection

Lü

Zhou

et al. 2013

JAD

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Hyperphosphorylation of tau occurs in preclinical and clinical stages of Alzheimer's disease (AD), and hyperphosphorylated tau is the main constituent of the paired helical filaments in the brains of mild cognitive impairment and AD patients. While most of the work described so far focused on the relationship between hyperphosphorylation of tau and microtubule disassembly as well as axonal transport impairments, both phenomena ultimately leading to cell death, little work has been done to study the correlation between tau hyperphosphorylation and DNA damage. As we showed in this study, tau hyperphosphorylation and DNA damage co-occurred under formaldehyde treatment in N2a cells, indicating that phosphorylated tau (p-Tau) induced by formaldehyde may be involved in DNA impairment. After phosphorylation, the effect of tau in preventing DNA from thermal denaturation was diminished, its ability to accelerate DNA renaturation was lost, and its function in protecting DNA from reactive oxygen species (ROS) attack was impaired. Thus, p-Tau is not only associated with the disassembly of the microtubule system, but also plays a crucial role in DNA impairment. Hyperphosphorylation-mediated dysfunction of tau protein in prevention of DNA structure from damage under the attack of ROS may provide novel insights into the mechanisms underlying tauopathies.

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Section: Discussionmentioning

confidence: 99%

Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection

Lü

Zhou

et al. 2013

JAD

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“…These monomers are not neurotoxic and are found in plasma, CSF, and interstitial fluid (ISF). In vitro, placed in saline, they spontaneously form soluble oligomers of 3-50 A␤ monomers, then soluble protofibrils, and finally fibrils whose rate increases with time; A␤ 42 oligomerizes more rapidly than A␤ 40 [18,19].…”

Section: A␤ 42 Metabolismmentioning

confidence: 99%

“…In patients with AD, the turnover decline has the same order of magnitude as in idiopathic NPH, but the effects of CSF stasis are potentiated by the decline in the ability of CSF to inhibit the formation of oligomers [18]. Indeed, in vitro, A␤ 42 monomers placed in saline form spontaneously oligomers within a few hours.…”

Section: Csf An Agent Of Admentioning

confidence: 99%

“…This oligomerization is greatly reduced when the saline is replaced by CSF of control subjects; however, it decreases very little when it is replaced with the CSF of patients with AD. The CSF of healthy controls seems to contain some elements that inhibit the formation of oligomers [18,92] and effectively the rates of A␤ 42 binding proteins are reduced in the CSF from AD, especially the CSF levels of cystatin C, betatrace, and TTR, three molecules synthesized by CPs [63,93].…”

Section: Csf An Agent Of Admentioning

confidence: 99%

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A Possible Role for CSF Turnover and Choroid Plexus in the Pathogenesis of Late Onset Alzheimer's Disease

Sérot

Zmudka

Jouanny

2012

JAD

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According to the amyloid theory, the appearance of amyloid-β (Aβ) deposits represents a pivotal event in late onset Alzheimer's disease (LOAD). Physiologically, Aβ42 monomers are cleaned by capillary resorption, enzymatic catabolism, and cerebrospinal fluid (CSF) transport. Factors that promote the oligomerization of Aβ42 must be specified. In vitro, these monomers spontaneously form neurotoxic oligomers whose rate increases with time suggesting that the stasis of CSF favors the oligomerization. In animals, experimental hydrocephalus generates CSF stasis followed by the appearance of amyloid deposits. In normal pressure hydrocephalus, amyloid deposits are common, especially in elderly patients, and the turnover decline has the same order of magnitude as in AD. In this disease, the effects of CSF stasis are potentiated by the decline in the ability of CSF to inhibit the formation of oligomers. CSF originates from choroid plexus (CP). In LOAD, the functions of secretion, synthesis, and transport of CP are impaired and this is related to morphological modifications. These impairments favor the decrease of CSF turnover, the diminished levels of transthyretin, a sequestering protein synthesized by CP, and the oligomerization of Aβ42. They are potentiated by a reduced enzymatic catabolism and a decreased capillary reabsorption of Aβ42, both alterations being related to age.

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“…2004; Ono and Yamada 2007). CSF from AD patients promotes formation of such fibrils (Ono et al. 2007).…”

Section: Res In Other Cns Disorders: Protection Of Spinal Vs Supra‐smentioning

confidence: 99%

Is the modulation of retinoid and retinoid‐associated signaling a future therapeutic strategy in neurological trauma and neurodegeneration?

Malaspina

Michael‐Titus

2007

Journal of Neurochemistry

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The complex molecular pathways that mediate the effects of vitamin A and its derivatives, are increasingly recognized as a component of the repair capacity that could be activated to induce protection and regeneration in the mature nervous tissue. Retinoid and retinoid-associated signaling plays an essential role in normal neurodevelopment and appears to remain active in the adult CNS. In this paper, we review evidence which supports the hypothesis of an activation of retinoid-associated signaling molecular pathways in the mature nervous tissue and its significance in the context of neurodegenerative, trauma-induced and psychiatric disorders, at spinal and supra-spinal levels. Finally, we summarize the potential therapeutic avenues based on the modulation of retinoid targets undergoing reactivation under conditions of acute injury and chronic degeneration in the central nervous system, and discuss some of the unresolved issues linked to this treatment strategy.

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P4–023: Cerebrospinal fluid of Alzheimer patients promotes beta–amyloid fibril formation in vitro

Cited by 5 publications

References 0 publications

Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection

Hyperphosphorylation Results in Tau Dysfunction in DNA Folding and Protection

A Possible Role for CSF Turnover and Choroid Plexus in the Pathogenesis of Late Onset Alzheimer's Disease

Is the modulation of retinoid and retinoid‐associated signaling a future therapeutic strategy in neurological trauma and neurodegeneration?

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