Beyond Amyloid – Widening the View on Alzheimer's Disease

Behl, Christian; Ziegler, Christine

doi:10.1111/jnc.14137

Cited by 21 publications

(17 citation statements)

References 7 publications

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“…Study strengths include detailed neuropsychological assessment, core biomarker processing laboratory, and comprehensive covariate ascertainment. Emphasizing biomarkers beyond the amyloid cascade hypothesis [29] offers an opportunity to enhance our understanding of concomitant pathological pathways driving adverse cognitive aging. Limitations include the cross-sectional design precluding inferences about causality.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Osborn

Khan

Kresge

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage. Methods Plasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n = 333, 73 ± 7 years; CSF n = 149, 72 ± 6 years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership, and Framingham Stroke Risk Profile. Results Plasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head‐to‐head comparison models. Discussion Plasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non‐demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Osborn

Khan

Kresge

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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“…Thus, the current neuropathological diagnosis of AD dementia is in fact a diagnosis of a working hypothesis of disease aetiology (for historical comments regarding the formation of the initial diagnostic guidelines in 1984/1985 see [ 144 ]). Additionally, as we discuss throughout, a litany of data has consistently emerged to question the robustness of the Aβ-centric view of AD dementia, leading to a loss of confidence in the amyloid hypothesis by many researchers [ 14 , 38 , 40 , 43 , 148 , 185 , 204 , 253 , 272 ].…”

Section: The Current Neuropathological Diagnosis Of Ad Propagates a Hmentioning

confidence: 99%

Questions concerning the role of amyloid-β in the definition, aetiology and diagnosis of Alzheimer’s disease

2018

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The dominant hypothesis of Alzheimer’s disease (AD) aetiology, the neuropathological guidelines for diagnosing AD and the majority of high-profile therapeutic efforts, in both research and in clinical practice, have been built around one possible causal factor, amyloid-β (Aβ). However, the causal link between Aβ and AD remains unproven. Here, in the context of a detailed assessment of historical and contemporary studies, we raise critical questions regarding the role of Aβ in the definition, diagnosis and aetiology of AD. We illustrate that a holistic view of the available data does not support an unequivocal conclusion that Aβ has a central or unique role in AD. Instead, the data suggest alternative views of AD aetiology are potentially valid, at this time. We propose that an unbiased way forward for the field, beyond the current Aβ-centric approach, without excluding a role for Aβ, is required to come to an accurate understanding of AD dementia and, ultimately, an effective treatment.Electronic supplementary materialThe online version of this article (10.1007/s00401-018-1918-8) contains supplementary material, which is available to authorized users.

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“…According to the recent statistics, there are more than 44 million dementia patients worldwide in 2017 and the number will rise to 131.5 million by 2050, which will cause a serious social and economic burden. Deposition of amyloid plaques, neurofibrillary tangles (NFTs) and the neuronal loss are the three hall markers of AD [ 3 - 7 ]. In addition, oxidative stress, inflammation, mitochondria dysfunction and increased cholesterol levels are all mechanisms that have been associated with Alzheimer's disease [ 8 , 9 ].…”

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confidence: 99%

Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway

Zhao¹,

Li²,

Gaur³

et al. 2020

Aging and disease

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The most common form of dementia is Alzheimer's disease which is characterized by memory loss and cognitive disorders. The pathogenesis of Alzheimer's disease is not known at present but toxicity of amyloidbeta is one of the central hypotheses. Amyloid-beta can stimulate the production of reactive oxygen species (ROS), cause oxidative stress, damage mitochondrial, cause inflammatory reactions and activate apoptosis related factors which lead to the neuronal death. In this study, we found that artemisinin, a first line antimalarial drug used in clinic for decades, improved the cognitive functions in Alzheimer's disease animal model 3xTg mice. Further study showed that artemisinin reduced the deposition of amyloid-beta and tau protein, reduced the release of inflammation factors and apoptosis factors, and thereby reduced the neuronal cell death. Western blot assay showed that artemisinin stimulated the activation of ERK/CREB signaling pathway. Consistent with these results, artemisinin concentration-dependently promoted the survival of SH-SY5Y cell against toxicity of amyloid-beta protein 1-42 induced ROS accumulation, caspase activation and apoptosis. Artemisinin also stimulated the phosphorylation of ERK1/2 and CREB in SH-SY5Y cells in time and concentration-dependent manner. Inhibition of ERK/CREB pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells in vitro as well as in vivo animal model 3xTg mice via, at least in part, the activation of the ERK/CREB pathway. Our findings also strongly support the potential of artemisinin as a new multi-target drug that can be used for preventing and treating the Alzheimer's disease.

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Beyond Amyloid – Widening the View on Alzheimer's Disease

Cited by 21 publications

References 7 publications

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Questions concerning the role of amyloid-β in the definition, aetiology and diagnosis of Alzheimer’s disease

Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway

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