Alzheimer’s disease, neural stem cells and neurogenesis: cellular phase at single-cell level

Alzheimer’s disease cannot be cured as of yet.Our current understanding on the causes of Alzheimer’s disease is limited.To develop treatments,experimental models that represent a particular cellular phase of the disease and more rigorous scrutiny of the cellular pathological mechanisms are crucial.In recent years,Alzheimer’s disease research underwent a paradigm shift.According to this tendency,Alzheimer’s disease is increasingly being conceived of a disease where not only neurons but also multiple cell types synchronously partake to manifest the pathology.Knowledge on every cell type adds an alternative approach and hope for the efforts towards the treatment.Neural stem cells and their neurogenic ability are making an appearance as a new aspect of the disease manifestation based on the recent findings that neurogenesis reduces dramatically in Alzheimer’s disease patients compared to healthy individuals.Therefore,understanding how neural stem cells can form new neurons in Alzheimer’s disease brains holds an immense potential for clinics.However,this provocative idea requires further evidence and tools for investigation.Recently,single cell sequencing appeared as a revolutionary tool to understand cellular programs in unprecedented resolution and it will undoubtedly facilitate comprehensive investigation of different cell types in Alzheimer’s disease.In this mini-review,we will touch upon recent studies that use single cell sequencing for investigating cellular response in Alzheimer’s disease and some consideration pertaining to the utilization of neural regeneration for Alzheimer’s disease research.

Investigation of human organoid retina with digital holographic transmission matrix measurements

Advanced manufacturing of retinal organoid samples from human induced pluripotent stem cells represents a promising way to study the development of retinal diseases.The retina is an epithelium composed of different cell layers with unique optical properties and detects light by photoreceptor neurons for visual function.There are still many challenges in detecting early and distinct cellular changes in retinal disease.In this paper,we study the capability of the optical transmission matrix,which fully describes the transition of a light field propagating through a scattering sample.Despite its rich information content,the transmission matrix is commonly just used for light delivery through scattering media.Digital holography is employed to measure the complex light-field information of the transmitted light.We demonstrate that singular value decomposition of the transmission matrix allows to discriminate phantom tissues with varying scattering coefficient.We apply these findings to retinal organoid tissues.Application of the protonophore carbonyl cyanide m-chloro-phenylhydrazone(CCCP),a known inducer of retinal damage in animals,caused cell death and structural changes in human retinal organoids,which resulted in distinct changes in the transmission matrix.Our data indicate that the analysis of the transmission matrix can distinguish pathologic changes of the retina towards the development of imaging-based biomarkers.