Beeta-amyloidi oligomerisoi fibrinogeeniä

ja stimuloi omaa fibrillien muodostamistaan fibrinogeeni-interaktion  avulla. 
http://www.pnas.org/content/107/50/21812.full
 results indicate that the fibrinogen oligomers are unstable. Therefore, the fibrinogen oligomer might be an intermediate state during the Aβ-induced fibrinogen aggregation process. Fibrinogen deposition with or without conversion to fibrin increases inflammation and vascular permeability where it is deposited (18, 19). Increased levels of fibrinogen alter vascular reactivity and impair endothelial cell layer integrity by binding to endothelial cell membrane receptors (17, 31). Taken together, the Aβ–fibrinogen interaction could reduce fibrin degradation and induce fibrinogen deposition in blood vessels. Both persistent fibrin and fibrinogen oligomer deposits in blood vessels may increase inflammation and cause neurovascular damage.

Protein misfolding and aggregation are hallmarks of several neurodegenerative disorders (32, 33), exemplified by Aβ in AD (1). Our study shows that Aβ can alter the physical properties and induce the aggregation of an entirely different protein (fibrinogen) as well as induce its own fibrillization. Although Aβ42 binds both fibrinogen and FragD, Aβ42 induced oligomerization of only fibrinogen, not FragD. This result indicates that Aβ42 binding itself is not enough to induce oligomerization of a binding partner and that fibrinogen is a specific target for Aβ-induced oligomerization. Fibrinogen has two identical ends (FragDs), and Aβ42 may bind at each. The symmetrical shape of fibrinogen with two binding sites could be the reason why Aβ42 induces oligomerization of only fibrinogen and not FragD.

Overall, the interaction between Aβ and fibrinogen caused fibrinogen oligomerization, promoted fibrin(ogen) deposition, as well as increased Aβ fibrillization. This study, combined with our previous work, suggests that the interaction between Aβ and fibrinogen may be an important contributor to AD pathogenesis. The development of AD therapies has been hampered thus far by the lack of a defined pathological mechanism in AD. Our discovery suggests a unique mechanism for AD and a unique target (fibrinogen) for AD treatment. Molecules that block this pathological interaction could restore the normal structure of the fibrin clot and could be used as therapeutic agents for AD without affecting normal blood clotting.

 http://www.ncbi.nlm.nih.gov/pubmed/20547128

Plasminogeeni -plasmiinifunktio tehottomampi Alzheimerin taudissa

http://www.nature.com/embor/journal/v4/n12/full/7400021.html

 The existence of two groups of AD patients with different plasmin levels suggests that disease-associated features such as inflammation or cell death are not responsible for plasmin paucity. This view is reinforced by the fact that the amount of amyloid plaques and tau filament aggregation are similar for all AD samples (see supplementary material and Table 1). Furthermore, variables such as age, sex, post-mortem brain sampling delay, hippocampal area analysed, degree of dementia or cause of death could also not be correlated to the alteration observed. On the other hand, we observed that all individuals with normal plasmin levels, AD and non-AD, carried either the E3/E3 or E3/E2 alleles of the apolipoprotein E (ApoE), whereas all individuals with low plasmin content carried at least one ApoE4 allele, a known risk factor for AD (Corder et al., 1993). Although these data point to the existence of a link between AD ApoE4 and low plasmin, it is beyond the scope of this work to determine if ApoE4 is a primary cause of this defect. Our goal remained to elucidate what cellular requirements might have failed in this group of patients.

Angiogeenisiä proteiinia verisuonissa AD taudissa

 Pro-angiogeeniset proteiinit koholla.
VEGF
Angiopoietiini Ang-2
MMPs, MMP-2, MMP-9
TIMP-1
Trombiini säätelee TIMP-1 korkeaksi.


J Alzheimers Dis. 2006 Sep;10(1):111-8. Angiogenic proteins are expressed by brain blood vessels in Alzheimer's disease.

Thirumangalakudi L, Samany PG, Owoso A, Wiskar B, Grammas P.

Source

Garrison Institute on Aging and Department of Neuropsychiatry and Behavioral Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

Abstract

Data are emerging to support the idea that mediators of angiogenesis are found in the Alzheimer's disease (AD) brain. The objective of this study is to compare the expression of the angiogenic mediators vascular endothelial growth factor (VEGF), angiopoietin, and matrix metalloproteinases (MMPs) in the microcirculation of AD patients and age-matched controls. Our results indicate that angiopoietin-2 and VEGF are expressed by AD- but not control-derived microvessels. AD-derived microvessels also release higher levels of MMP-2 and MMP-9 compared to controls. The data show that despite high levels of MMP-9, assessed by western blot, MMP-9 activity is not detectable in AD microvessels. In this regard we find high levels of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in AD, but not control vessels. Furthermore, we explore the ability of thrombin, previously shown to be present in AD microvessels, to affect TIMP expression in cultured brain endothelial cells and find that thrombin causes up regulation of TIMP-1. These data show that angiogenic changes occur in the microcirculation of the AD brain and suggest that if these changes are contributory to disease pathogenesis, targeting the abnormal brain endothelial cell would provide a novel therapeutic approach for the treatment of this disease.

Narkolepsia

http://psychiatry.stanford.edu/narcolepsy/faq1.html#2

Multimodaalinen integraatio

http://www.ncbi.nlm.nih.gov/pubmed/11997686

Neuroreport. 2002 May 7;13(6):779-83.

Spatial coincidence modulates interaction between visual and somatosensory evoked potentials.

Schürmann M, Kolev V, Menzel K, Yordanova J.

Source

Institute of Physiology, Medical University Lübeck, 23538 Lübeck, Germany.

Abstract

The time course of interaction between concurrently applied visual and somatosensory stimulation with respect to evoked potentials (EPs) was studied. Visual stimuli, either in the left or right hemifield, and electric stimuli to the left wrist were delivered either alone or simultaneously. Visual and somatosensory EPs were summed and compared to bimodal EPs (BiEP, response to actual combination of both modalities). Temporal coincidence of stimuli lead to sub-additive or over-additive amplitudes in BiEPs in several time windows between 75 and 275 ms. Additional effects of spatial coincidence (left wrist with left hemifield) were found between 75 and 300 ms and beyond 450 ms. These interaction effects hint at a temporo-spatial pattern of multiple brain areas participating in the process of multimodal integration.

KOMMENTTI: 
Olen nyt asettanut joitain  artikkeleita, jotka valaisevat aivojen keräämän muistiaineksen kertymistä ja  kronologisoitumista. Puu kasvaa ja tekee vuosirenkaita. Aivojen neuronaalinen kronobiologia tekee  muistijälkeä, jotka  multimodaalisesti  integroidaan ja vahvistetaan ja päivitetään monen aistiradan antaman informaation kautta ja tämän takia ihminen on jatkumossa: kokee elämänsä olevan  jatkumoa, ympäristönsä oelvan tilavuutta, jolla on jatkuvia omianisuuksia jne. 
Näyttää olevan  muuten aivan aktuellina aiheenakin PubMed artikkeleissa tuo timing kaikin tavoin.

Jos tämä funktio,  multifunktionaalinen jatkuvuus katkeaisi,  ihminen ei tulisi toimeen yhteiskunnassa eikä edes kotonaan, koska hän voisi unohtaa hetkestä toiseen kaiken olennaisen olemassaolon. 
Tämän takia tiedemiehet  selvittävät miten  muistijälki koostuu ja mitkä tekijät sitä vahvistavat  ja integroivat. Tietyisti  vanha hyvä neuvo on: kertaus on opintojen äiti.  Samanaikainen näkö  ja kuulohavainto vahvsitaa  havaintoa. Samoin  asian  sanominen ääneen tai jopa  laulaminen- jos asiaan sopii, vahvsitavat kaksin kerroin  jotain  integroitavaa. Samoin  objektin koskettaminen kådellä( hahmottaminen) tai esim  jonkin tekstin kirjoittaminen tuo myös lisää muistifunktiota.
Tässä voi sitten  pohtia , mitä merkitsee että nykyään tuskin kirjoitetaan kynällä, vaan sen sijaan naptutetaan tangenteilla   tekstiä.  Tietysti muistijälkeä tulee  tangentin naputtamisesta, kuten  viulunsoittamisesta  tai pianon soittamisesta.Kaikilla näillä erilaisilla funktioilla on jokin projektinsa aivoissa,  tapahtuu multimodaalista integroitumista.
Myöhemmin suomennan  näitä muistiin ottamiani artikkeleita.
Ihminen ei voi ladata muistia kuten puu puuainesta, vaan ihmisen muistiaines pitää kuitenkin  kerätä aivojen volyymiin paakoppaan, joten siellä täytyy olla hyvä aineenvaihdunta, jotta ollenaiset ja vitaalit  asiat ja henkilön  itsensä tärkeiksi  printaamat  asiat valiutuvat ja epäolennaiset  komprimoidaan biologisesti  tai poistetaan aineenvaihdunnalla.Muistissa toimii proteiinit.
22.10.2012

Laulaminen ja puhuminen

Neuroreport. 2000 Jun 26;11(9):1997-2000.

Opposite hemispheric lateralization effects during speaking and singing at motor cortex, insula and cerebellum.

Riecker A, Ackermann H, Wildgruber D, Dogil G, Grodd W.

Source

Department of Neuroradiology, University of Tuebingen, Germany.

Abstract

Aside from spoken language, singing represents a second mode of acoustic (auditory-vocal) communication in humans. As a new aspect of brain lateralization, functional magnetic resonance imaging (fMRI) revealed two complementary cerebral networks subserving singing and speaking. Reproduction of a non-lyrical tune elicited activation predominantly in the right motor cortex, the right anterior insula, and the left cerebellum whereas the opposite response pattern emerged during a speech task. In contrast to the hemodynamic responses within motor cortex and cerebellum, activation of the intrasylvian cortex turned out to be bound to overt task performance. These findings corroborate the assumption that the left insula supports the coordination of speech articulation. Similarly, the right insula might mediate temporo-spatial control of vocal tract musculature during overt singing. Both speech and melody production require the integration of sound structure or tonal patterns, respectively, with a speaker's emotions and attitudes. Considering the widespread interconnections with premotor cortex and limbic structures, the insula is especially suited for this task.

PMID:

10884059

[PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms

Näkö ja kuulohavaintojen integraatio lapsesta aikuiseen

Front Integr Neurosci. 2012;6:77. doi: 10.3389/fnint.2012.00077. Epub 2012 Sep 17.

Development of visuo-auditory integration in space and time.

Gori M, Sandini G, Burr D.

Source

Robotics, Brain and Cognitive Sciences Department, Istituto Italiano di Tecnologia Genoa, Italy.

Abstract

Adults integrate multisensory information optimally (e.g., Ernst and Banks, 2002) while children do not integrate multisensory visual-haptic cues until 8-10 years of age (e.g., Gori et al., 2008). Before that age strong unisensory dominance occurs for size and orientation visual-haptic judgments, possibly reflecting a process of cross-sensory calibration between modalities. It is widely recognized that audition dominates time perception, while vision dominates space perception. Within the framework of the cross-sensory calibration hypothesis, we investigate visual-auditory integration in both space and time with child-friendly spatial and temporal bisection tasks. Unimodal and bimodal (conflictual and not) audio-visual thresholds and PSEs were measured and compared with the Bayesian predictions. In the temporal domain, we found that both in children and adults, audition dominates the bimodal visuo-auditory task both in perceived time and precision thresholds. On the contrary, in the visual-auditory spatial task, children younger than 12 years of age show clear visual dominance (for PSEs), and bimodal thresholds higher than the Bayesian prediction. Only in the adult group did bimodal thresholds become optimal. In agreement with previous studies, our results suggest that also visual-auditory adult-like behavior develops late. We suggest that the visual dominance for space and the auditory dominance for time could reflect a cross-sensory comparison of vision in the spatial visuo-audio task and a cross-sensory comparison of audition in the temporal visuo-audio task.