Partial rescue of memory deficits induced by calorie restriction in a mouse model of tau deposition

Brownlow, Milene; Joly‐Amado, Aurélie; Azam, Sana; Elza, Mike; Selenica, Maj Linda B.; Pappas, Colleen; Small, Brent J.; Engelman, Robert W.; Gordon, Marcia N.; Morgan, Dave

doi:10.1016/j.bbr.2014.06.001

Cited by 61 publications

(55 citation statements)

References 44 publications

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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%

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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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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“…Activity testing for open field, revealed a genotype effect but no treatment effect; no differences were noted between the treated mice and controls when comparing tau-depositing transgenic mice to non-transgenic littermates (Table 4). Cognitive assessment (as in Brownlow et al, 2014) did reveal performance improvements in both novel object recognition testing (Figure 4) and radial arm water maze (RAWM – Figure 5) in response to MC-1 treatment when compared to IgG1 treated mice.…”

Section: Recent Work In Our Laboratorymentioning

confidence: 97%

“…Concurrent with the tau pathology is neuronal loss and atrophy. Behaviorally these mice exhibit extreme hyperactivity and impairment in a large number of cognitive function tests (Brownlow et al, 2014)…”

Section: Recent Work In Our Laboratorymentioning

confidence: 99%

“…Four days post-injection, tissue was collected for IHC and histological staining to compare tau-pathology markers between the groups. NFTs were identified using Gallyas silver staining (Brownlow et al 2014). We also examined total tau using the rabbit polyclonal antibody H150 (Santa Cruz), rabbit-anti pSer199/202 (AnaSpec), and rabbit-anti pSer396 (AnaSpec).…”

Section: Recent Work In Our Laboratorymentioning

confidence: 99%

“…The mice where implanted with mini-osmotic pumps (Alzet) filled with 20 μg of either MC-1, Tau 5, or TOMA, or IgG control, (all of which were 1 mg/ml) into the right lateral ventricle for continuous delivery of 0.5 μg a day over 28 days, using mini-osmotic pumps (Alzet) as described previously (Selenica et al, 2013, Brownlow et al, 2014). This route of administration allowed for behavioral testing as well as pathology evaluation.…”

Section: Recent Work In Our Laboratorymentioning

confidence: 99%

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Tau-Directed Immunotherapy: A Promising Strategy for Treating Alzheimer’s Disease and Other Tauopathies

Schroeder

Joly‐Amado

Gordon

et al. 2015

J Neuroimmune Pharmacol

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Immunotherapy directed against tau is a promising treatment strategy for Alzheimer’s Disease (AD) and tauopathies. We review initial studies on tau-directed immunotherapy, and present data from our laboratory testing antibodies using the rTg4510 mouse model, which deposits tau in forebrain neurons. Numerous antibodies have been tested for their efficacy in treating both pathology and cognitive function, in different mouse models, by different routes of administration, and at different ages or durations. We report, here, that the conformation-specific antibody MC-1 produces some degree of improvement to both cognition and pathology in rTg4510. Pathological improvements as measured by Gallyas staining for fully formed tangles and phosphorylated tau appeared four days after intracranial injection into the hippocampus. We also examined markers for microglial activation, which did not appear impacted from treatment. Behavioral effects were noted after continuous infusion of antibodies into the lateral ventricle for approximately 2 weeks. We examined basic motor skills, which were not impacted by treatment, but did note cognitive improvements with both novel object and radial arm water maze testing. Our results support earlier reports in the initial review presented here, and collectively show promise for this strategy of treatment. The general absence of extracellular tau deposits may avoid the opsonization and phagocytosis mechanisms activated by antibodies against amyloid, and make anti tau approaches a safer method of immunotherapy for Alzheimer’s disease.

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Cachexia and advanced dementia

Minaglia

Giannotti

Boccardi

et al. 2019

J cachexia sarcopenia muscle

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Cachexia is a complex metabolic process that is associated with several end‐stage organ diseases. It is known to be also associated with advanced dementia, although the pathophysiologic mechanisms are still largely unknown. The present narrative review is aimed at presenting recent insights concerning the pathophysiology of weight loss and wasting syndrome in dementia, the putative mechanisms involved in the dysregulation of energy balance, and the interplay among the chronic clinical conditions of sarcopenia, malnutrition, and frailty in the elderly. We discuss the clinical implications of these new insights, with particular attention to the challenging question of nutritional needs in advanced dementia and the utility of tube feeding in order to optimize the management of end‐stage dementia.

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Partial rescue of memory deficits induced by calorie restriction in a mouse model of tau deposition

Cited by 61 publications

References 44 publications

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

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

Tau-Directed Immunotherapy: A Promising Strategy for Treating Alzheimer’s Disease and Other Tauopathies

Cachexia and advanced dementia

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