Clinical Research on Alzheimer’s Disease: Progress and Perspectives

Sun, Baoqing; Li, Weiwei; Zhu, Chi; Jin, Wang-Sheng; Zeng, Fan; Liu, Yuhui; Bu, Xian‐Le; Zhu, Jie; Yao, Xiu-Qing; Wang, Yanjiang

doi:10.1007/s12264-018-0249-z

Cited by 111 publications

(70 citation statements)

References 52 publications

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“…; Sun et al. ; Vina & Sanz‐Ros ). One of the most important reasons for these unsuccessful trials may have been the timing: most trials were focused on people already suffering from clinically evident dementia, where brain damage is in more advanced stages (Sun et al.…”

Section: Introductionmentioning

confidence: 99%

“…One of the most important reasons for these unsuccessful trials may have been the timing: most trials were focused on people already suffering from clinically evident dementia, where brain damage is in more advanced stages (Sun et al. ; Vina & Sanz‐Ros ). As reversing neuronal damage may be impossible, it may be more effective to start treatment before the onset of dementia (Kumar et al.…”

Section: Introductionmentioning

confidence: 99%

“…The development of a new non‐invasive, patient friendly and easily repeatable measurement of a biomarker for pre‐clinical AD patients is especially interesting, because it would allow for early interventions targeting the causes at a stage that neuronal damage could still be prevented (Sun et al. ; Vina & Sanz‐Ros ).…”

Section: Introductionmentioning

confidence: 99%

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Retinal layer thickness in preclinical Alzheimer's disease

Kreeke

Nguyen

Haan

et al. 2019

Acta Ophthalmologica

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Purpose: There is urgent need for non-invasive diagnostic biomarkers in the preclinical phase of Alzheimer's Disease (AD). Several studies suggest that retinal thickness is reduced in AD. Here, we aim to test the diagnostic value of retinal thickness in preclinical AD, as defined by cognitively normal individuals with amyloid pathology on PET. Methods: One hundred and sixty five cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the European Medical Information Framework for Alzheimer's Disease PreclinAD study. Participants underwent [ 18 F] flutemetamol PET that was visually rated for presence or absence of cortical amyloid beta (Ab). Binding potential (BP ND ) was calculated as continuous measure for Ab. Spectral Domain OCT was used to asses total and individual inner retinal layer thickness in the macular region (ETDRS circles) as well as peripapillary retinal nerve fibre layer (pRNFL) thickness. Differences between Ab+ and AbÀ individuals and associations between BP ND and retinal thickness were analyzed. Results: No differences were found in retinal layer thickness in the macula or pRNFL between Ab+ and AbÀ individuals. A positive associations between BP ND and macular total retinal thickness was observed in the inner ring (p = 0.018), but this was not statistically significant after correction for multiple testing (p = 0.144). Brain/eye parameters had moderate to high intra-twin correlations (p < 0.001) except visual rating score of Ab, which did not correlate (r = 0.21, p = 0.068). Conclusion: Variation in retinal thickness likely reflects genetic differences between individuals, but cannot discriminate between healthy and preclinical AD cases, making its use as biomarker in these early stages limited.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Retinal layer thickness in preclinical Alzheimer's disease

Kreeke

Nguyen

Haan

et al. 2019

Acta Ophthalmologica

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“…One of the research areas supported is biomarker research, aiming at measuring diseaserelated bodily parameters. While AD biomarkers are still far from standard clinical tools, the expectation put forward by funding agencies and involved researchers is that, at some point, they will be widely available and significantly improve, first of all, diagnostic certainty and precision and, further, contribute to prediction, improved prognosis, and development of drugs (Jack et al 2011;Sun et al 2018). Tau PET is one such envisioned biomarker for AD.…”

Section: Tau Pet Imaging As Emergent Tool For Ad Diagnosis and Prognosismentioning

confidence: 99%

Subtle voices, distant futures: a critical look at conditions for patient involvement in Alzheimer’s biomarker research and beyond

Nielsen

Boenink

2019

Journal of Responsible Innovation

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Patient involvement is increasingly regarded a key part of responsible innovation (RI) in biomedicine. The high expectations to participation call not only for methodological experiments, but also for critical analyses of the conditions and products of participatory practices. Based on an experiment with involving patients in Alzheimer's disease biomarker research, we identify and reflect on two key conditions in patient involvement that we summarize as 'subtle voices' and 'distant futures'. The former refers to the hesitance and knowledge hierarchies that participants may enact and/or experience; the latter refers to the challenges of imagining elusive technologies and future practices, not least in the light of an illness that fundamentally changes the meaning of time. We argue that while our case may be exceptionally challenging, it provides a valuable lens for illuminating these key conditions that promotors and facilitators of patient participation in, especially, early-stage innovation processes should acknowledge and address. ARTICLE HISTORY

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“…Moreover photo-active chlorin 6 dye was also found to reduce the aggregation by modulating the histidine residues (Leshem et al 2019). Methylene blue derived Leuco-methylthioninium Bis (Hydromehanesulphonate) (LMTM) entered phase-3 clinical trial for treatment of mild Alzheimer's disease (Wilcock et al 2018), however LMTM in further studies was found to be ineffective (Sun et al 2018). Toluidine Blue (TB) is a basic phenothiazine dye having structural similarity with methylene blue.…”

Section: Introductionmentioning

confidence: 99%

Photo-excited Toluidine Blue disaggregates the Repeat Tau and modulates cytoskeletal structure in neuronal cells

Dubey

Gorantla

Chinnathambi

2020

Preprint

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Alzheimer's disease is a progressive neurological disorder characterized by the intracellular accumulation of Tau protein aggregates. Inhibition of protein aggregation by photo-excited dyes is emerging as novel strategy for the treatment of certain diseases. Toluidine Blue is a basic phenothiazine dye having potency of photo-excitation by irradiation with red light at 630±20 nm. In present work, we studied the effect of Toluidine Blue and photo-excited TB on aggregation of repeat Tau in-vitro using Thioflavin S fluorescence assay, SDS-PAGE and electron microscopy. Results show that TB efficiently inhabited the formation of higher order aggregates. Moreover, the photoexcited TB led to disaggregation of the mature repeat Tau fibrils. Further, studies on the effect of Toluidine blue on cell viability and cytoskeleton network of Neuro2acells show that TB was not toxic to neuronal cells at lower concentrations but at high concentrations (> 5 µM) both TB and photoexcited TB induced significant toxicity . Immunofluorescence studies on the cytoskeleton of Neuro2a cells show that Toluidine Blue and photo-excited Toluidine Blue treatment at non-toxic concentration of 0.5 µM stimulated formation of actin rich lamellipodia and filopodia structures. Tubulin networks were also differentially modulated after the treatment of Toluidine Blue and photoexcited Toluidine Blue. End Binding protein 1 (EB1) levels were observed to increase after Toluidine Blue and photo-excited Toluidine Blue treatment indicating the accelerated microtubule polymerization. The overall study suggested that Toluidine Blue inhibited the aggregation of soluble Tau and photo-excited Toluidine Blue disaggregated the pre-formed Tau filaments. 2

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Clinical Research on Alzheimer’s Disease: Progress and Perspectives

Cited by 111 publications

References 52 publications

Retinal layer thickness in preclinical Alzheimer's disease

Retinal layer thickness in preclinical Alzheimer's disease

Subtle voices, distant futures: a critical look at conditions for patient involvement in Alzheimer’s biomarker research and beyond

Photo-excited Toluidine Blue disaggregates the Repeat Tau and modulates cytoskeletal structure in neuronal cells

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