An article published by Aileen l. Pogue of Alchem ​​Biotech Research in Canada and his colleagues at Louisiana State University discuss a pro-inflammatory toxin that may contribute to the development of Alzheimer's disease. The results are published in Frontiers in Neurology.

This article is (as usual) aggressively promoted, but probably not as new or important as its promoters would hope, nevertheless the subject is interesting even though it has made the subject of numerous scientific publications.

Intestinal dysbiosis has been implicated in the pathogenesis and progression of Alzheimer's disease by initiating and prolonging neuroinflammatory processes. Gut microbiota metabolites appear to be critical in the gut-brain axis mechanism. Gut microbiota metabolites, such as trimethylamine n-oxide, lipopolysaccharide, and short-chain fatty acids, are suggested to mediate systemic inflammation and intracerebral amyloidosis via endothelial dysfunction. New data suggest that the fungal microbiota may also influence the pathology of Alzheimer's disease.

Pogue and his colleagues believe they have found evidence that the lipopolysaccharide molecule in the human gastrointestinal (GI) tract generates an endotoxin which can perturb cells in the brain. Their paper links several recent observations linking lipopolysaccharide-induced increase in NF-kB signaling to increase in microRNA-30b.

NF-κB plays a key role in regulating the immune response to infection. Improper regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in synaptic plasticity and memory processes.

MicroRNAs (miRNAs) are short non-coding RNAs that are involved in post-transcriptional regulation of gene expression by affecting both stability and translation of mRNAs. MicroRNAs are thought to have regulatory roles through complementarity with mRNA. These microRNAs regulate a number of genes associated with breast cancer.

The authors show that an increase in miRNA-30b is able to decrease the expression of neuron-specific neurofilament light chain (NFL) messenger RNA in stressed human neuronal-glial cells cultures.

Neurofilaments provide structural support to axons and regulate axon diameter, which influences nerve conduction velocity. Neurofilament light chain depletion therefore disrupts the normal shape of neuronal cells, their cytoarchitecture and synaptic organization. Neurofilament light chains are a useful marker for monitoring disease in amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, and more recently Huntington's disease.

The presence of endotoxins, when detected in the blood, is called endotoxemia. Endotoxemia is associated with obesity, diet, cardiovascular disease and diabetes.

There is experimental and observational evidence that lipopolysaccharide may play a role in depression. Administration of lipopolysaccharide in mice can lead to depressive symptoms, and there appear to be elevated levels of lipopolysaccharide in some people with depression. Inflammation can sometimes play a role in the development of depression, and lipopolysaccharide is pro-inflammatory.

Finally, lipopolysaccharide-induced inflammation can induce cellular senescence, as has been demonstrated for lung epithelial cells and microglial cells (the latter leading to neurodegeneration).

In this study, researchers detail the pathway of BF-lipopolysaccharide from the gut to the brain and its mechanisms of action once there. For them, BF-lipopolysaccharide leaks out of the gastrointestinal tract, crosses the blood-brain barrier via the circulatory system and gains access to the cerebral compartments. Next, it increases inflammation in brain cells and inhibits neuron-specific neurofilament light (NF-L), a protein that supports cellular integrity.

A deficiency of this protein leads to progressive atrophy of neuronal cells, and ultimately to cell death, as seen in neurons affected by Alzheimer's disease. They also report that an adequate intake of dietary fiber can prevent the process.

Indeed, 60% of gut microbiome variation is attributable to diet. Therefore, modulating the gut microbiome through dietary means could be an effective approach to reduce the risk of Alzheimer's disease.

Data from animal studies have suggested that dietary fat acts as the primary macronutrient responsible for postprandial endotoxemia, and that the quantity and quality of dietary fat differentially influence metabolic endotoxemia.

Additionally, healthy diets high in unsaturated fatty acids have been associated with lower circulating levels of lipopolysaccharide, which is strongly associated with lower pro-inflammatory markers. Conversely, consumption of diets high in energy or saturated fat has been associated with increased postprandial levels of lipopolysaccharide and increased circulating levels of pro-inflammatory markers.

Since people do not eat single nutrients and instead consume a diverse range of foods and a combination of nutrients that are likely to be interacting, studying the effects of whole diets offers the possibility of accounting for the interactions between different nutrients. It is also probable that introducing variety in diet helps in having a diverse microbiome. Yet has people age, digestion becomes more difficult and aging people often prefer to not change their diet.

Thus, dietary habits may be more predictive of a real effect on the gut microbiome and Alzheimer's disease risk than foods or nutrients taken in isolation.

On sait depuis 2017 que certaines personnes atteintes de diabète de type 2 ont un risque plus élevé de développer la maladie d'Alzheimer.

Une variante de l'un des principaux gènes impliqués dans la maladie d'Alzheimer: APOE4, semble interférer avec la capacité des cellules cérébrales à utiliser l'insuline, ce qui peut éventuellement provoquer le stress (en quelque sorte l'état de famine) et la mort des cellules nerveuses. Officieusement, on appelle parfois cela: Le diabète de type 3.

L'insuline régule le métabolisme des glucides, des lipides et des protéines en favorisant l'absorption du glucose du sang par le foie, les graisses et les cellules musculaires squelettiques.

Des concentrations élevées d'insuline dans le sang inhibent fortement la production et la sécrétion de glucose par le foie. L'insuline circulante affecte également la synthèse des protéines (augmentation de la masse tissulaire) dans une grande variété de tissus.

A l'inverse, de faibles niveaux d'insuline dans le sang ont l'effet inverse en favorisant un catabolisme (fonte des tissus) généralisé, en particulier de la graisse corporelle de réserve.

On pense que chez personnes diabétiques, l'utilisation ou la signalisation de l'insuline par leur cerveau ne fonctionne pas. Leur risque de développer la maladie d'Alzheimer est environ 10 à 15 fois plus élevé.

Ce nouvel article de Gemma Salvadó et ses collègues apporte davantage d'informations sur ce sujet.

L'activation gliale (les cellules nerveuses autres que les neurones) est l'un des premiers mécanismes à être altérés dans la maladie d'Alzheimer.

La protéine acide fibrillaire gliale (GFAP) est une protéine protéine de filament intermédiaire (IF) qui est exprimée par de nombreux types de cellules du système nerveux central (SNC), y compris les astrocytes.

Il existe de multiples troubles associés à une mauvaise régulation de la GFAP, et une blessure peut provoquer une réaction néfaste des cellules gliales. La cicatrisation gliale est une conséquence de plusieurs conditions neurodégénératives, ainsi que des blessures qui sectionnent le matériel neural. La cicatrice est formée par des astrocytes interagissant avec le tissu fibreux pour rétablir les marges gliales autour du noyau central de la lésion et est partiellement causée par une régulation à la hausse de la GFAP.

La protéine acide fibrillaire gliale est liée à l'astrogliose réactive (la destruction des astrocytes, des cellules nerveuses différentes des neurones) et peut être mesurée à la fois dans le liquide céphalo-rachidien et le sang.

Il a été suggéré que la GFAP plasmatique soit modifiée plus tôt dans la maladie d'Alzheimer que son homologue du liquide céphalo-rachidien.

Bien que les astrocytes consomment environ la moitié de l'énergie dérivée du glucose dans le cerveau, la relation entre l'astrogliose réactive et le métabolisme cérébral du glucose est mal comprise. Le fluorodésoxyglucose (FDG) est un analogue du glucose marqué avec un isotope émetteur de positrons (18F) qui permet de mesurer la consommation cérébrale régionale de glucose à l'aide de la tomographie par émission de positons (TEP).

Les auteurs espagnols visaient à étudier l'association entre l'absorption de fluorodésoxyglucose (FDG) et l'astrogliose réactive, au moyen de GFAP quantifié à la fois dans le plasma et le liquide céphalo-rachidien pour les mêmes participants. GFAP est une protéine de filament intermédiaire astrocytaire, principalement exprimée dans le cerveau.

La cohorte ALFA a caractérisé la maladie d'Alzheimer préclinique chez 2743 individus sans troubles cognitifs, âgés de 45 à 75 ans, et enrichie pour les antécédents familiaux de maladie d'Alzheimer sporadique. Dans cette cohorte de parents, 419 participants ALFA +  ont été sélectionnés pour être préférentiellement porteurs d'APOE-ε4 et/ou pour être des enfants adultes de patients AD. Ces participants ont subi une évaluation plus complète incluant une ponction lombaire et une TEP Aβ et [18F]FDG.

Pour cette étude, les auteurs ont inclus 314 participants sans troubles cognitifs de la cohorte ALFA+, dont 112 étaient positifs à l'amyloïde-β. Les associations entre les marqueurs GFAP et l'absorption de [18F]FDG ont été étudiées. Les auteurs ont également cherché à savoir si ces associations étaient modifiées par le statut Aβ et tau.

La GFAP plasmatique était positivement associée à la consommation de glucose dans tout le cerveau, tandis que les associations de GFAP du liquide céphalo-rachidien avec l'absorption de [18F]FDG n'ont été observées que dans des zones spécifiques plus petites comme le pôle temporal et le lobe temporal supérieur.

Ces associations ont persisté lors de la prise en compte des biomarqueurs de la pathologie Aβ, mais sont devenues négatives chez les participants Aβ-positifs et tau-positifs dans des domaines similaires de l'hypométabolisme lié à la maladie d'Alzheimer.

Une réactivité astrocytaire plus élevée, probablement en réponse aux changements pathologiques précoces de la maladie d'Alzheimer, est liée à une consommation de glucose plus élevée. Avec l'apparition de la pathologie tau, le découplage observé entre les biomarqueurs astrocytaires et la consommation de glucose pourrait indiquer une incapacité à maintenir les demandes énergétiques plus élevées requises par les astrocytes réactifs.

Lisez l'article original sur Pubmed

It's known since some time that there is a link between blood and Alzheimer disease.

For example in 2019, after being dosed with GRF6021, a drug proposed by Alkahest, a California-based startup, Alzheimer's patients in a clinical trial retained memory and mental function for six months - when they would normally be expected to deteriorate. GRF6021, a drug proposed by Alkahest, a California-based startup, is made from the blood of young people.

On contrary a large study found that people who experienced a blood transfusion may be at risk of Alzheimer's disease or may be, because they were transfused with "old blood".

A research team led by Claudio Soto, in the Department of Neurology with McGovern Medical School at UTHealth Houston, with Akihiko Urayama, as first author, performed a series of whole blood exchange treatments to partially replace blood from mice exhibiting Alzheimer's disease-causing amyloid precursor proteins with complete blood from healthy mice of the same genetic background.

The results of the study was published in Molecular Psychiatry.

The development of cerebral amyloid plaques in a transgenic mice model of AD (Tg2576) was significantly reduced by 40–80% through exchanging whole blood with normal blood from wild type mice having the same genetic background. Importantly, such reduction resulted in improvement in spatial memory performance in aged Tg2576 mice.

The exact mechanism by which blood exchange reduces amyloid pathology and improves memory is presently unknown, but measurements of Aβ in plasma soon after blood exchange suggest that mobilization of Aβ from the brain to blood may be implicated.

Their results suggest that a target for AD therapy may exist in the peripheral circulation, which could open a novel disease-modifying intervention for AD. Technologies commonly used in medical practice, such as plasmapheresis or blood dialysis, could 'clean' blood from Alzheimer's patients, reducing the buildup of toxic substances in the brain.

This was suggested recently.

Plasma-based biomarkers (blood tests) present a promising approach in the research and clinical practice of Alzheimer's disease as they are inexpensive, accessible and minimally invasive. Recent studies have demonstrated the prognostic utility of plasma biomarkers of Alzheimer pathology or neurodegeneration, such as pTau-181 and NF-L, yet they do not enable to predict cognitive decline.

In this new publication, scientists conducted an observational cohort study to determine the prognostic utility of plasma biomarkers in predicting progression to dementia for individuals presenting with mild cognitive impairment due to probable Alzheimer's disease.

The scientists used an improved Elisa assay to measure the level of 460 circulating proteins in banked plasma samples of all participants. The authors used a discovery data set comprised 60 individuals with mild cognitive impairment and a validation data set consisting of 21 stable and 21 progressors.

They developed a machine learning model to distinguish progressors from stable and used 44 proteins with significantly different plasma levels in progressors versus stable along with age, sex, education and baseline cognition as candidate features.

A model with age, education, APOE genotype, baseline cognition, plasma pTau-181 and 12 plasma Olink protein biomarker levels was able to distinguish progressors from stable with 86.7% accuracy.

In the validation data set, the model accuracy was 78.6%. The Olink proteins selected by the model included those associated with vascular injury and neuroinflammation.

In addition, to compare these prognostic biomarkers to those that are altered in Alzheimer's disease or other types of dementia relative to controls, the authors analyzed samples from 20 individuals with Alzheimer, 30 with non-Alzheimer dementias and 34 with normal cognition.

The proteins NF-L and PTP-1B were significantly higher in both Alzheimer and non-Alzheimer dementias compared with cognitively normal individuals.

Interestingly, the prognostic markers of decline at the mild cognitive impairment stage did not overlap with those that differed between dementia and control cases.

In summary, authors' findings suggest that plasma biomarkers of inflammation and vascular injury are associated with cognitive decline. Developing a plasma biomarker profile could aid in prognostic deliberations and identify individuals at higher risk of dementia in clinical practice.

Aging is an important risk factor for neurodegenerative disorders (neurodegenerative disorders), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD ).

Protein synthesis has historically been described as decreasing with age, although not all studies agree and often point to high organ and tissue variability. Protein degradation is also commonly described as compromised in aging

Analysis of brain protein levels in the physiologically aged brain, however, showed only minor changes in protein abundance in the older adult brain compared to the young adult brain. However, a recent theory indicates that the alterations observed in neurodegenerative disorders could be linked to the minimization of proteomic costs, reflecting a new prioritization of bioenergetic costs, which would preserve the most "expensive" proteins in energy from the aged brain while replacing more easily metabolically less expensive proteins.

To test this theory, it is interesting to study protein turnover, which regulates the balance between protein synthesis and degradation, because it could be particularly affected by aging and could lead to changes prelude to neuropathology. The turnover of proteins begins with their destruction, the catabolism of proteins is a key function of the digestive process. The amino acids resulting from these proteins thus degraded can be transformed into fuel for the Krebs cycle/citric acid (TCA).

Researchers led by Anja Schneider of the German Center for Neurodegenerative Diseases in Bonn and Eugenio Fornasiero of the University Medical Center Göttingen, both in Germany, measured the half-lives of more than 3,500 proteins in mouse brain. They found an average increase of 20 percent with age.

For Alzheimer's disease, these life-extending proteins included:

• the group of Tau proteins (MAPT)
• ADAM10 which is correlated with the appearance of different types of synaptopathies, ranging from neurodevelopmental disorders, i.e. autism spectrum disorders, to neurodegenerative diseases, i.e. Alzheimer's disease.
• DBN1 A decrease in the amount of this protein in the brain has been implicated as a possible contributing factor in the pathogenesis of memory impairment in Alzheimer's disease.
• CTSDs which are implicated in the pathogenesis of several diseases, including breast cancer and possibly Alzheimer's disease.

For Parkinson's disease, they included:

• Alpha-synuclein, a protein which in humans is encoded by the SNCA gene. Alpha-synuclein is a neuronal protein that regulates synaptic vesicle trafficking and the subsequent release of neurotransmitters. It is abundant in the brain, while smaller amounts are found in the heart, muscle, and other tissues. In the brain, alpha-synuclein is found primarily in the axon terminals of presynaptic neurons.

  Alpha-synuclein aggregates to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. These disorders are known as synucleinopathies.

• PARK7, Under oxidative conditions, the deglycase protein DJ-1 inhibits the aggregation of α-synuclein via its chaperone activity, thus functioning as a redox-sensitive chaperone and as an oxidative stress sensor. The functional protein DJ-1 has been shown to bind to metals and protect against metal-induced cytotoxicity of copper and mercury. Defects in this gene cause early-onset autosomal recessive Parkinson's disease

For ALS, they included:

• TUBA4A, The alpha-4A chain of tubulin is a protein which in humans is encoded by the TUBA4A gene. This gene has only rarely been associated with ALS. Overall, ALS-related genes can be categorized into four groups based on the cellular pathways in which they are involved: (1) protein homeostasis; (2) homeostasis and RNA trafficking; (3) cytoskeletal dynamics; and (4) mitochondrial function.

  The reason TUBA4A might be associated with ALS is that motor neurons and skeletal muscle cells are known to be the largest cells in the human body. The significant length of these cells makes them highly dependent on the correct architecture of the cytoskeleton, the integrity of which is essential for the axonal transport necessary to maintain the integrity of synapses. Several mutations in the tubulin beta-4A (TUBA4A) gene destabilize microtubules by impairing repolymerization, likely contributing to axonal degeneration in MN.

• SOD1, whose protective role against oxidative stress has been well studied, but whose mutations were previously only associated with 25% cases of familial ALS.

Conclusion The authors of this article observed a previously unknown alteration in proteostasis that is correlated with parsimonious protein turnover with high biosynthetic costs, revealing a global metabolic adaptation that preludes neurodegeneration.

However, nothing in this study explains how malformed, poorly localized proteins might appear. This study only shows a correlation between the half-life of proteins and certain neurodegenerative diseases.

Their results suggest that future therapeutic paradigms, aimed at addressing these metabolic adaptations, may be able to delay the onset of neurodegenerative disorders.

Among these we could mention certain factors related to metabolism which determine the half-life of proteins such as pH and temperature. It is well known that aging cells have an increasing pH: They become basic. when the daughter cells come from an aging mother cell, the daughter's age is "reset". A parent cell becomes less acidic as the parent cell ages. Daughter cells, on the other hand, have very acidic vacuoles.

Le vieillissement est un facteur de risque important pour les troubles neurodégénératifs (troubles neurodégénératifs), y compris la maladie d'Alzheimer (MA), la maladie de Parkinson (MP), la sclérose latérale amyotrophique (SLA) et la maladie de Huntington (HD).

La synthèse des protéines a été historiquement décrite comme diminuant avec l'âge, bien que toutes les études ne soient pas d'accord et indiquent souvent une forte variabilité des organes et des tissus. La dégradation des protéines est également communément décrite comme compromise dans le vieillissement

L'analyse des niveaux de protéines cérébrales dans le cerveau physiologiquement âgé n'a pourtant montré que des modifications mineures de l'abondance des protéines dans le cerveau de l'adulte âgé par rapport au cerveau du jeune adulte. Cependant une théorie récente indique que les altérations observées dans les troubles neurodégénératifs pourraient être liées à la minimisation des coûts protéomiques, reflétant une nouvelle priorisation des coûts bioénergétiques, qui préserverait les protéines les plus "couteuses" en énergie du cerveau âgé tout en remplaçant plus facilement les protéines métaboliquement moins couteuses.

Pour tester cette théorie, il est intéressant d'étudier le renouvellement des protéines, qui régule l'équilibre entre la synthèse et la dégradation des protéines, car il pourrait être particulièrement affecté par le vieillissement et pourrait conduire à des changements prélude à la neuropathologie. Le renouvellement des protéines commence par leur destruction, le catabolisme des protéines est une fonction clé du processus de digestion. Les acides aminé issus de ces protéines ainsi dégradés peuvent être transformés en carburant pour le cycle de Krebs/acide citrique (TCA).

Des chercheurs dirigés par Anja Schneider du Centre allemand pour les maladies neurodégénératives de Bonn et Eugenio Fornasiero du Centre médical universitaire de Göttingen, tous deux en Allemagne, ont mesuré les demi-vies de plus de 3 500 protéines dans le cerveau de souris. Ils ont trouvé une augmentation moyenne de 20 pour cent avec l'âge.

Pour la maladie d'Alzheimer, ces protéines à vie allongées comprenaient:

• le groupe des protéines Tau (MAPT)
• ADAM10 qui est corrélée à l'apparition de différents types de synaptopathies, allant des troubles neurodéveloppementaux, c'est-à-dire les troubles du spectre autistique, aux maladies neurodégénératives, c'est-à-dire la maladie d'Alzheimer.
• DBN1 Une diminution de la quantité de cette protéine dans le cerveau a été impliquée comme facteur contributif possible dans la pathogenèse des troubles de la mémoire dans la maladie d'Alzheimer.
• CTSD qui sont impliqués dans la pathogenèse de plusieurs maladies, dont le cancer du sein et éventuellement la maladie d'Alzheimer.

Pour la maladie de Parkinson, ils comprenaient:

• L'alpha-synucléine, une protéine qui chez l'homme, est codée par le gène SNCA. L'alpha-synucléine est une protéine neuronale qui régule le trafic des vésicules synaptiques et la libération ultérieure de neurotransmetteurs. Elle est abondante dans le cerveau, tandis que de plus petites quantités se trouvent dans le cœur, les muscles et d'autres tissus. Dans le cerveau, l'alpha-synucléine se trouve principalement dans les terminaisons axonales des neurones présynaptiques.

  L'alpha-synucléine s'agrège pour former des fibrilles insolubles dans des conditions pathologiques caractérisées par des corps de Lewy, telles que la maladie de Parkinson, la démence à corps de Lewy et l'atrophie multisystématisée. Ces troubles sont connus sous le nom de synucléinopathies.

• PARK7, Dans des conditions oxydatives, la protéine déglycase DJ-1 inhibe l'agrégation de l'α-synucléine via son activité chaperonne, fonctionnant ainsi comme chaperon sensible à l'oxydoréduction et comme capteur de stress oxydatif. Il a été démontré que la protéine fonctionnelle DJ-1 se lie aux métaux et protège contre la cytotoxicité induite par les métaux du cuivre et du mercure. Les défauts de ce gène sont à l'origine de la maladie de Parkinson autosomique récessive à début précoce

Pour la SLA, ils comprenaient:

• TUBA4A, La chaîne alpha-4A de la tubuline est une protéine qui chez l'homme, est codée par le gène TUBA4A. Ce gène a été seulement rarement associé à la SLA. Dans l'ensemble, les gènes liés à la SLA peuvent être classés en quatre groupes selon les voies cellulaires dans lesquelles ils sont impliqués : (1) homéostasie des protéines ; (2) homéostasie et trafic d'ARN; (3) dynamique du cytosquelette ; et (4) fonction mitochondriale.

  La raison pour laquelle TUBA4A pourrait être associé à la SLA est que les motoneurones et les cellules des muscles squelettiques sont connus pour être les plus grandes cellules du corps humain. La longueur importante de ces cellules les rend fortement dépendants de la bonne architecture du cytosquelette, dont l'intégrité est essentielle pour le transport axonal nécessaire au maintien de l'intégrité des synapses. Plusieurs mutations du gène de la tubuline bêta-4A (TUBA4A) déstabilisent les microtubules en altérant la repolymérisation, contribuant probablement à la dégénérescence axonale du MN.

• SOD1, dont le rôle protecteur contre le stress oxidatif a été bien étudié, mais dont les mutations étaient auparavant seulement associé à 25% cas de SLA familiale.

Conclusion Les auteurs de cet article ont observé une altération jusque-là inconnue de la protéostase qui est corrélée au renouvellement parcimonieux des protéines avec des coûts biosynthétiques élevés, révélant une adaptation métabolique globale qui prélude à la neurodégénérescence.

Cependant rien dans cette étude n'explique comment les protéines malformés, mal localisés pourraient apparaître. Cette étude ne montre qu'une corrélation entre la demi-vie de protéines et certaines maladies neurodégénératives.

Leurs résultats suggèrent que les futurs paradigmes thérapeutiques, visant à répondre à ces adaptations métaboliques, pourraient être en mesure de retarder l'apparition du troubles neurodégénératifs.

Parmi ceux-ci on pourrait évoquer certains facteurs liés au métabolisme qui déterminent la demi-vie des protéines comme le pH et la température. Il est bien connu que les cellules vieillissantes ont un pH qui augmente: Elles deviennent basiques. lorsque les cellules filles proviennent d'une cellule mère vieillissante, l'âge de la fille est « remis à zéro ». Une cellule mère devient moins acide à mesure que la cellule mère vieillit. Les cellules filles, en revanche, ont des vacuoles très acides.

Here we report about a study which is a bit unusual. The reason it appears on this blog is not because its efficiency which is doubtful, but because of the need to investigate new areas. And there is a significant body of publications on this topic.

If you browse through Aliexpress health devices you will probably find weird devices supposed to be inserted in your nose, ear or worn at your wrist that heal from many diseases such as diabetes or aging with infrared light or magnetic stimulation.

The authors of several acupuncture departments from Beijing, Wuhan, Guangzhou, propose to use Transauricular vagal nerve stimulation (taVNS) at 40 Hz to attenuate hippocampal amyloid load in transgenic mice models of Alzheimer.

The auricular branch of the vagus nerve supplies sensory innervation to the skin of the ear canal, tragus, and auricle.

Classical vagus nerve stimulation involves surgical implantation of electrodes onto the cervical branch of the vagus nerve. Electrical pulses are delivered to the vagus nerve via an implanted pulse generator surgically implanted in the chest.

Vagus nerve stimulation is currently FDA-approved for epilepsy, refractory depression, and chronic obesity and long-term safety of Vagus nerve stimulation is well established.

Transauricular vagal nerve stimulation on the other hand, delivers electrical stimulation to the auricular branch of the vagus nerve (ABVN), an easily accessible target that innervates the human ear.

There is a western commercial device which do just that.

Yet it's not clear what is meant by 40 Hz electical stimulation. 40 Hz is a "magical" frequency often involved in Alzheimer stimulation but there is no clear why it should be effective. In other publications different protocols have been used and were quite successful, for example 1 mA, 20 Hz, 30 s ON and 5 min OFF, the total length of 30 min, with a 320 μs pulse width.

The scientists say their results show that 40-Hz taVNS inhibits the hippocampal P2X7R/NLRP3/Caspase-1 signaling and improves spatial learning and memory in 6-month-old APP/PS1 mice. Yet they used a variety of immunofluorescence, immunohistochemistry, and various staining/blotting techniques which are not very precise, so "more studies are needed".

Read the original article on Pubmed

There is a close link between iron and polyamine biosynthesis and metabolism. In a recent study, the authors reported alterations in the serum levels of hepcidin and other iron-related proteins in Alzheimer's disease patients. Hepcidin is a key regulator of the entry of iron into the circulation in mammals.

Iron plays a crucial role in many physiological processes of the human body. Early studies found iron overload is directly proportional to cognitive decline in Alzheimer's disease. Amyloid precursor protein (APP) and tau protein, both of which are related to the Alzheimer's disease pathogenesis, are associated with brain iron metabolism.

Polyamines are ubiquitous molecules, which, like iron, are essential for cell growth. All eukaryotic cells are equipped with a specific polyamine transport system (PTS). Polyamines have primary and secondary amino groups which chelate bivalent metal cations such as Fe and Cu.

Based on these findings, this pilot study compared serum levels of one of the polyamines, Spermidine, between Alzheimer's disease, mild cognitive impairment, and control subjects, correlating the levels with the existing clinical and neuroimaging data.

This cross-sectional study measured Spermidine levels in frozen serum samples of 43 Alzheimer's disease patients, 12 patients with Mild Cognitive Impairement (MCI) patients, and 21 age-matched controls, provided by the Oregon Alzheimer's Disease Center Bio-repository.

MCI patients showed significantly higher mean Spermidine serum levels compared to controls, with a non-significant trend for higher Spermidine serum levels in pure Alzheimer's disease participants compared to controls.

Furthermore, Spermidine serum levels correlated with serum levels of the chief iron regulatory protein, hepcidin in Alzheimer's disease participants with a more advanced disease stage.

These, and other results, demonstrate that the cell polyamine transport system is a potential cell entry pathway for iron. The studied polyamines, spermine and spermidine, may be components of the pool of transferrin-independent iron-chelating vectors, which have recently attracted the attention of many investigators.

Read the original article on Pubmed