Body mass index is associated with biological CSF markers of core brain pathology in Alzheimer's disease

Jawaid, Ali; Leske, Henning; Neumann, Manuela

doi:10.1016/j.neurobiolaging.2011.12.012

Cited by 69 publications

(61 citation statements)

References 6 publications

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“…In contrast, stimulation paradigms with fewer stimuli or lower amplitude currents reveal that aged rats have deficits in LTP induction in CA1 and in the dentate gyrus [62–64]. Studies in rats and mice have also shown that aged animals display deficits in LTP maintenance and that the durability of LTP correlates with performance in hippocampal dependent tasks [65–67]. Furthermore, LTP is reduced in the hippocampus of aged rats that demonstrate cognitive impairments relative to aged unimpaired rats [68,69].…”

Section: Synaptic Plasticity and Cognitionmentioning

confidence: 99%

Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease

Hullinger

Puglielli

2017

Behavioural Brain Research

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As the population of people aged 60 or older continues to rise, it has become increasingly important to understand the molecular basis underlying age-related cognitive decline. In fact, a better understanding of aging biology will help us identify ways to maintain high levels of cognitive functioning throughout the aging process. Many cellular and molecular aspects of brain aging are shared with other organ systems; however, certain age-related changes are unique to the nervous system due to its structural, cellular and molecular complexity. Importantly, the brain appears to show differential changes throughout the aging process, with certain regions (e.g. frontal and temporal regions) being more vulnerable than others (e.g. brain stem). Within the medial temporal lobe, the hippocampus is especially susceptible to age-related changes. The important role of the hippocampus in age-related cognitive decline and in vulnerability to disease processes such as Alzheimer’s disease has prompted this review, which will focus on the complexity of changes that characterize aging, and on the molecular connections that exist between normal aging and Alzheimer’s disease. Finally, it will discuss behavioral interventions and emerging insights for promoting healthy cognitive aging.

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Section: Synaptic Plasticity and Cognitionmentioning

confidence: 99%

Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease

Hullinger

Puglielli

2017

Behavioural Brain Research

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“…Consequences of axonal trafficking inhibition are linked to altered synaptic transmission, inadequate neurotrophic factor support, altered mitochondrial fission and fusion that eventually leads to the loss of energy production and neuronal death (Calkins et al, 2011; Calkins and Reddy, 2011; Itoh et al, 2013; Reddy et al, 2010; Schwarz, 2013; Yao and Brinton, 2011; Ye et al, 2012). Despite significant research efforts, the underlying molecular mechanism(s) of axonal trafficking inhibition remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Axonal trafficking is also essential for delivering damaged mitochondria to the soma for degradation (Lin et al, 2017). Mounting data generated in tissue and cells from AD patients and in animal models of FAD suggest mitochondrial axonal trafficking is affected early in the disease prior to the onset of memory impairment or the development of amyloid plaques (Correia et al, 2016; Galindo et al, 2010; Pigino et al, 2003; Selfridge et al, 2013; Tillement et al, 2011; Trushina et al, 2012; Yao et al, 2009; Ye et al, 2012). We have previously demonstrated that bidirectional inhibition of mitochondrial trafficking was already observed in embryonic neurons from different mouse models with familial AD mutations prior to the formation of aggregated endogenous Aβ peptides (Trushina et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Differential effect of amyloid beta peptides on mitochondrial axonal trafficking depends on their state of aggregation and binding to the plasma membrane

Zhang

Trushin

Christensen

et al. 2018

Neurobiology of Disease

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Inhibition of mitochondrial axonal trafficking by amyloid beta (Aβ) peptides has been implicated in early pathophysiology of Alzheimer’s Disease (AD). Yet, it remains unclear whether the loss of motility inevitably induces the loss of mitochondrial function, and whether restoration of axonal trafficking represents a valid therapeutic target. Moreover, while some investigations identify Aβ oligomers as the culprit of trafficking inhibition, others propose that fibrils play the detrimental role. We have examined the effect of a panel of Aβ peptides with different mutations found in familial AD on mitochondrial motility in primary cortical mouse neurons. Peptides with higher propensity to aggregate inhibit mitochondrial trafficking to a greater extent with fibrils inducing the strongest inhibition. Binding of Aβ peptides to the plasma membrane was sufficient to induce trafficking inhibition where peptides with reduced plasma membrane binding and internalization had lesser effect on mitochondrial motility. We also found that Aβ peptide with Icelandic mutation A673T affects axonal trafficking of mitochondria but has very low rates of plasma membrane binding and internalization in neurons, which could explain its relatively low toxicity. Inhibition of mitochondrial dynamics caused by Aβ peptides or fibrils did not instantly affect mitochondrial bioenergetic and function. Our results support a mechanism where inhibition of axonal trafficking is initiated at the plasma membrane by soluble low molecular weight Aβ species and is exacerbated by fibrils. Since trafficking inhibition does not coincide with the loss of mitochondrial function, restoration of axonal transport could be beneficial at early stages of AD progression. However, strategies designed to block Aβ aggregation or fibril formation alone without ensuring the efficient clearance of soluble Aβ may not be sufficient to alleviate the trafficking phenotype.

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“…For example, randomized controlled trials have produced conflicting results as to whether fish oil supplementation can enhance cognitive performance or mitigate cognitive decline in adults [11,13,14]. These conflicting results are surprising given that observational studies have been far more consistent in suggesting that n -3 fatty acid blood composition is associated with cognitive outcomes [15,16,17,18].…”

Section: Discussionmentioning

confidence: 99%

Randomized Controlled Trial Examining the Effects of Fish Oil and Multivitamin Supplementation on the Incorporation of n-3 and n-6 Fatty Acids into Red Blood Cells

et al. 2014

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The present randomized, placebo-controlled, double-blind, parallel-groups clinical trial examined the effects of fish oil and multivitamin supplementation on the incorporation of n-3 and n-6 fatty acids into red blood cells. Healthy adult humans (n = 160) were randomized to receive 6 g of fish oil, 6 g of fish oil plus a multivitamin, 3 g of fish oil plus a multivitamin or a placebo daily for 16 weeks. Treatment with 6 g of fish oil, with or without a daily multivitamin, led to higher eicosapentaenoic acid (EPA) composition at endpoint. Docosahexaenoic acid (DHA) composition was unchanged following treatment. The long chain LC n-3 PUFA index was only higher, compared to placebo, in the group receiving the combination of 6 g of fish oil and the multivitamin. Analysis by gender revealed that all treatments increased EPA incorporation in females while, in males, EPA was only significantly increased by the 6 g fish oil multivitamin combination. There was considerable individual variability in the red blood cell incorporation of EPA and DHA at endpoint. Gender contributed to a large proportion of this variability with females generally showing higher LC n-3 PUFA composition at endpoint. In conclusion, the incorporation of LC n-3 PUFA into red blood cells was influenced by dosage, the concurrent intake of vitamin/minerals and gender.

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Body mass index is associated with biological CSF markers of core brain pathology in Alzheimer's disease

Cited by 69 publications

References 6 publications

Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease

Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease

Differential effect of amyloid beta peptides on mitochondrial axonal trafficking depends on their state of aggregation and binding to the plasma membrane

Randomized Controlled Trial Examining the Effects of Fish Oil and Multivitamin Supplementation on the Incorporation of n-3 and n-6 Fatty Acids into Red Blood Cells

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