Metabolic changes over the course of aging in a mouse model of tau deposition

Joly‐Amado, Aurélie; Serraneau, Karisa; Brownlow, Milene; Evsikova, Caralina Marín de; Speakman, John R.; Gordon, Marcia N.; Morgan, Dave

doi:10.1016/j.neurobiolaging.2016.04.013

Cited by 38 publications

(30 citation statements)

References 67 publications

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“…Body weight and food intake were measured at each injection time, to identify whether the treatments were altering either of these metabolic measures. We noted that the Tg4510 mice consumed significantly more food, but also exhibited a significant reduction in body weight likely due to their excessive activity as described previously [20, 21]. However, neither body weight nor food intake was modified by the antibody treatment.…”

Section: Methodssupporting

confidence: 81%

Oligomeric tau-targeted immunotherapy in Tg4510 mice

et al. 2017

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BackgroundFinding ways to reverse or prevent the consequences of pathogenic tau in the brain is of considerable importance for treatment of Alzheimer’s disease and other tauopathies. Immunotherapy against tau has shown promise in several mouse models. In particular, an antibody with selectivity for oligomeric forms of tau, tau oligomer monoclonal antibody (TOMA), has shown rescue of the behavioral phenotype in several murine models of tau deposition.MethodsIn this study, we examined the capacity of TOMA to rescue the behavioral, histological, and neurochemical consequences of tau deposition in the aggressive Tg4510 model. We treated mice biweekly with 60 μg TOMA i.p. from 3.5 to 8 months of age.ResultsNear the end of the treatment, we found that oligomeric tau was elevated in both the CSF and in plasma. Further, we could detect mouse IgG in Tg4510 mouse brain after TOMA treatment, but not after injection with mouse IgG1 as control. However, we did not find significant reductions in behavioral deficits or tau deposits by either histological or biochemical measurements.ConclusionsThese data suggest that there is some exposure of the Tg4510 mouse brain to TOMA, but it was inadequate to affect the phenotype in these mice at the doses used. These data are consistent with other observations that the rapidly depositing Tg4510 mouse is a challenging model in which to demonstrate efficacy of tau-lowering treatments compared to some other preclinical models of tau deposition/overexpression.

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Section: Methodssupporting

confidence: 81%

Oligomeric tau-targeted immunotherapy in Tg4510 mice

et al. 2017

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“…Metabolic deregulations in animal models of tauopathies resemble those found in patients with Tau-related dementia. Indeed, decreased body weight has been described in a mouse model of Tau deposition such as THY-22 [148] or Tg4510 [149, 150], sometimes despite increased feeding behavior [151]. Additionally, genetic deletion of Tau resulted in increased body weight [152].…”

Section: Brain Insulin Resistance In Ad and Tauopathies: Cause Or Conmentioning

confidence: 99%

“…Impaired satiation and increased feeding behavior [153], as well as changes in body temperature [154] were also observed in a mouse model combining amyloid plaques and Tau pathology (3xTgAD). In Tg4510 mice, weight loss was specific to fat mass and co-occurred with deregulation of metabolic rate [151] as well as disturbances in circadian rhythm [98]. In both cases, Tau pathology was found in the hypothalamus.…”

Section: Brain Insulin Resistance In Ad and Tauopathies: Cause Or Conmentioning

confidence: 99%

Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

et al. 2018

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Alzheimer disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments, and lower brain glucose metabolism, which often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood. Insulin is a hormone involved in the control of energy homeostasis both peripherally and centrally, and insulin-resistant state has been linked to increased risk of dementia. It is now well established that insulin resistance can exacerbate Tau lesions, mainly by disrupting the balance between Tau kinases and phosphatases. On the other hand, the emerging literature indicates that Tau protein can also modulate insulin signalling in the brain, thus creating a detrimental vicious circle. The following review will highlight our current understanding of the role of insulin in the brain and its relation to Tau protein in the context of AD and tauopathies. Considering that insulin signalling is prone to be pharmacologically targeted at multiple levels, it constitutes an appealing approach to improve both insulin brain sensitivity and mitigate brain pathology with expected positive outcome in terms of cognition.

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“…est associée à une progression accélérée de la maladie, à un taux plus élevé d'institutionnalisation et à une mortalité accrue. Dans les modèles de maladie d'Alzheimer, cette perte de poids est retrouvée chez les animaux présentant une Tauopathie [24][25][26], parfois en dépit d'une prise alimentaire accrue [27]. Ces pertes de poids n'apparaissent pas à proprement parler en lien avec une résistance centrale à l'insuline.…”

Section: Tableau I Récapitulatif Des Lésions Hypothalamiques Rencontunclassified

Relation mutuelle entre Tau et signalisation centrale de l’insuline

et al. 2018

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La maladie d’Alzheimer (MA) est une maladie neurodégénérative caractérisée par des déficits cognitifs et des lésions neuropathologiques (agrégats de Tau et plaques amyloïdes), mais également par des troubles métaboliques et neuroendocriniens. Les mécanismes à l’origine de ces processus physiopathologiques demeurent mal compris mais pourraient provenir du développement d’une insulino-résistance centrale. L’altération de l’action de l’insuline dans le cerveau des patients atteints de MA a été décrite comme facteur aggravant les lésions Tau et amyloïdes ainsi que les troubles cognitifs. L’origine de cette résistance centrale est bien moins comprise mais ferait intervenir la protéine Tau, suggérant l’existence d’un cercle vicieux contribuant à l’apparition et à la progression des signes cliniques. La présente revue vise à faire le point sur notre compréhension actuelle du rôle de l’insuline dans le cerveau et de sa relation avec la protéine Tau dans la MA et les Tauopathies.

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Metabolic changes over the course of aging in a mouse model of tau deposition

Cited by 38 publications

References 67 publications

Oligomeric tau-targeted immunotherapy in Tg4510 mice

Oligomeric tau-targeted immunotherapy in Tg4510 mice

Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

Relation mutuelle entre Tau et signalisation centrale de l’insuline

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