P1‐240: Glutamatergic (VGLUT1) synapses are not lost in Alzheimer's disease cerebral cortex, but preferentially accumulate amyloid‐beta and p‐tau pathology

Sokolow, Sophie; Luu, Sanh H.; Vinters, Harry V.; Miller, Carol A.; Gylys, Karen H.

doi:10.1016/j.jalz.2010.05.791

Cited by 3 publications

(2 citation statements)

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“…Elles entraînent des phénomènes inflammatoires et oxydatifs, avec comme conséquence la mort des neurones. Elles suractivent, par ailleurs, les MAP kinases chargées de contrôler la phosphorylation des protéines Tau ; la dégénérescence neurofibrillaire due à l'augmentation de la phosphorylation des protéines Tau qui se détachent des microtubules et s'agrègent en amas de neurofibrilles (Perl, 2010), avec comme conséquence la dégénérescence neuronale ; l'excitotoxicité neuronale glutamatergique (Walton & Dodd, 2007), probablement liée à la localisation préférentielle des peptides Aβ et phospho-Tau dans les synaptosomes glutamatergiques (Sokolow et al, 2010), entraînant une entrée excessive de calcium dans le neurone post-synaptique et aboutissant à des phénomènes de nécrose et d'apoptose neuronales (Ankarcrona et al, 1995). Ces processus dégénératifs de mort neuronale sont à l'origine d'une atrophie cérébrale.…”

Section: Lésions Et Mécanismes Mis En Jeu Au Cours De La Maladie D'al...unclassified

Vitamine D et maladie d’Alzheimer : d’une curieuse idée à une possibilité de traitement

Annweiler

2014

Biologie Aujourd'hui

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Beyond the classically described regulation of calcium and bone metabolism, vitamin D is a neurosteroid hormone essential to neurophysiological function (regulation of neurotransmitters and neurotrophins) with anti-inflammatory and antioxidant neuroprotective action. In contrast, hypovitaminosis D, which is extremely frequent in the elderly, may result in neurological dysfunction and may explain part of the cognitive disorders in this population. Epidemiology is consistent with this notion and has repeatedly shown an association between hypovitaminosis D and cognitive decline, either in the general population or in Alzheimer's patients. Preliminary intervention trials confirm the causal relationship and quantify the cognitive effect of vitamin D supplementation in the elderly. This raises prospects for primary/secondary prevention of cognitive decline by exogenous supplies of vitamin D. In particular, although current anti-dementia drugs are only symptomatic, future treatment options could rely on drug combinations preventing several neurodegenerative mechanisms at once. As such, vitamin D enhances the efficacy of memantine in terms of neuronal protection and prevention of cognitive decline in Alzheimer's disease.

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Section: Lésions Et Mécanismes Mis En Jeu Au Cours De La Maladie D'al...unclassified

Vitamine D et maladie d’Alzheimer : d’une curieuse idée à une possibilité de traitement

Annweiler

2014

Biologie Aujourd'hui

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“…(3) Glutamatergic neuronal excitotoxicity, likely due to the preferential localization of amyloid beta peptides and phosphorylated Tau in glutamatergic synaptosomes [21,22] , leads to excessive calcium entry into the postsynaptic neuron, ending in neuronal necrosis and apoptosis [23,24] . The clinical consequence of these degenerative processes is a decline in cognitive function that mainly leads to learning and memory difficulties.…”

Section: Underlying Mechanismsmentioning

confidence: 99%

Vitamin D-Mentia: Randomized Clinical Trials Should Be the Next Step

Annweiler

Beauchet²

2011

Neuroepidemiology

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Hypovitaminosis D is highly prevalent in the elderly. Its possible role in the pathogenesis of Alzheimer’s disease (AD) is particularly important, as AD remains a public health concern with no current efficient treatment. Vitamin D administration could be a multitarget stabilizing treatment for AD since vitamin D simultaneously targets several factors leading to neurodegeneration through immunoregulatory, antioxidant and anti-ischemic actions, as well as the regulation of neurotrophic factors, acetylcholine neurotransmitter and clearance of amyloid beta peptide, and the avoidance of hyperparathyroidism. By preventing neuronal loss, the question is whether correcting hypovitaminosis D among older adults could also prevent AD-related cognitive decline. The cross-sectional associations between the vitamin D intakes – whether from diet, sun exposure or drug supplements – and cognition strengthened this hypothesis, but prevented the finding of a cause and effect link. Pre-post studies showed an improvement of cognition concomitant with the increase in 25-hydroxyvitamin D concentrations. One randomized trial found that supraphysiological doses of vitamin D were not better than physiological doses at improving cognition in AD. At this stage, only clinical trials testing vitamin D supplements versus placebo can further determine the impact of vitamin D administration on cognition and AD with higher levels of evidence.

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Possibility of a New Anti-Alzheimerʼs Disease Pharmaceutical Composition Combining Memantine and Vitamin D

Annweiler¹,

Beauchet²

2012

Drugs & Aging

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Alzheimer's disease (AD) is the leading cause of dementia. In addition to a decrease in brain cholinergic activity, AD is also marked by glutamatergic excitotoxicity that results in neuronal death, characterized clinically by a loss of learning and memory abilities. The currently available drugs for symptomatic treatment of AD (i.e. memantine and acetylcholinesterase inhibitors) only temporarily slow down the natural history of the disease process. Among them, memantine is the only one that acts as a non-competitive low-affinity modulator of N-methyl-D-aspartate (NMDA) receptors. Memantine's modulation of NMDA receptors has been reported to prevent the neuronal necrosis induced by glutamatergic calcium neurotoxicity, but not the neuronal apoptosis resulting from oxidative stress. This observation calls for new drug regimen strategies based on memantine combined with molecules having antioxidant effects, in order to create a multi-target therapy to increase neuronal protection and prevent AD progression. We wish to highlight that vitamin D is a secosteroid hormone that is suggested to have neuroprotective effects that include regulation of neuronal calcium homeostasis, as well as antioxidant, neurotrophic and anti-inflammatory properties. The combination of memantine plus vitamin D may provide, in one treatment, enhanced protection against several degenerative processes linked to AD. Based on the present rationale, a clinical trial testing this hypothesis is currently in recruitment (AD-IDEA trial; ClinicalTrials.gov identifier: NCT01409694). This new pharmaceutical composition may provide an effective solution to the problem of neuronal death and cognitive decline in AD.

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P1‐240: Glutamatergic (VGLUT1) synapses are not lost in Alzheimer's disease cerebral cortex, but preferentially accumulate amyloid‐beta and p‐tau pathology

Cited by 3 publications

References 0 publications

Vitamine D et maladie d’Alzheimer : d’une curieuse idée à une possibilité de traitement

Vitamine D et maladie d’Alzheimer : d’une curieuse idée à une possibilité de traitement

Vitamin D-Mentia: Randomized Clinical Trials Should Be the Next Step

Possibility of a New Anti-Alzheimerʼs Disease Pharmaceutical Composition Combining Memantine and Vitamin D

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