Role of the Extracellular Matrix in Alzheimer’s Disease

Sun, Yahan; Xu, Sen; Jiang, Ming; Liu, Xia; Ling, Yang; Bai, Zhan-Tao; Yang, Qinghu

doi:10.3389/fnagi.2021.707466

Cited by 67 publications

(66 citation statements)

References 135 publications

(141 reference statements)

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“…These pathways were downregulated in a disease state suggesting that cell morphology may be compromised in AD. All of these pathways have been associated with AD in previous studies (89)(90)(91). Overall, our data demonstrate the potential of patient-derived ONS cells to provide a cell-based model for AD.…”

Section: Discussionsupporting

confidence: 72%

An Alzheimer’s disease patient-derived olfactory cell model identifies gene expression changes associated with cognition

Rantanen

Bitar

Lampinen

et al. 2022

Preprint

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An early symptom of Alzheimer's disease (AD) is an impaired sense of smell, for which the molecular basis remains elusive. Here, we generated human olfactory neurosphere-derived (ONS) cells from people with AD and mild cognitive impairment (MCI), and performed global RNA sequencing to determine gene expression changes. ONS cells expressed markers of neuroglial differentiation, providing a unique cellular model to explore early AD-associated disease pathways. Our transcriptomics data from ONS cells revealed differentially expressed genes (DEGs) associated with cognitive processes in AD cells compared to MCI, or matched healthy controls (HC). A-Kinase Anchoring Protein 6 (AKAP6) was the most significantly altered gene in AD compared to both MCI and HC, and has been linked to cognitive function. The greatest change in gene expression of all DEGs occurred between AD and MCI. Gene pathway analysis revealed defects in multiple cellular processes with aging, intellectual deficiency and alternative splicing being the most significantly dysregulated in AD ONS cells. Our results demonstrate that ONS cells can provide a cellular model for AD that recapitulates disease-associated differences. We have revealed potential novel genes, including AKAP6 that may have a role in AD, particularly MCI to AD transition, and should be further examined.

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Section: Discussionsupporting

confidence: 72%

An Alzheimer’s disease patient-derived olfactory cell model identifies gene expression changes associated with cognition

Rantanen

Bitar

Lampinen

et al. 2022

Preprint

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Section: Discussionmentioning

confidence: 88%

An Alzheimer’s Disease Patient-Derived Olfactory Stem Cell Model Identifies Gene Expression Changes Associated with Cognition

Rantanen

Bitar

Lampinen

et al. 2022

Cells

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An early symptom of Alzheimer’s disease (AD) is an impaired sense of smell, for which the molecular basis remains elusive. Here, we generated human olfactory neurosphere-derived (ONS) cells from people with AD and mild cognitive impairment (MCI), and performed global RNA sequencing to determine gene expression changes. ONS cells expressed markers of neuroglial differentiation, providing a unique cellular model to explore changes of early AD-associated pathways. Our transcriptomics data from ONS cells revealed differentially expressed genes (DEGs) associated with cognitive processes in AD cells compared to MCI, or matched healthy controls (HC). A-Kinase Anchoring Protein 6 (AKAP6) was the most significantly altered gene in AD compared to both MCI and HC, and has been linked to cognitive function. The greatest change in gene expression of all DEGs occurred between AD and MCI. Gene pathway analysis revealed defects in multiple cellular processes with aging, intellectual deficiency and alternative splicing being the most significantly dysregulated in AD ONS cells. Our results demonstrate that ONS cells can provide a cellular model for AD that recapitulates disease-associated differences. We have revealed potential novel genes, including AKAP6 that may have a role in AD, particularly MCI to AD transition, and should be further examined.

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“…Their distribution throughout the cortex, for example, varies: they occur in the neo- but not in the entorhinal cortex [ 95 , 96 ]); furthermore, their density in the different neocortical areas is typical and differs [ 95 ]. Irrespective of location and surrounded cell type, the backbone of perineuronal nets is aggrecan [ 6 , 97 ], associated with hyaluronic acid and tenascins [ 7 , 98 , 99 , 100 , 101 ]. A row of classification studies investigated and attributed diverse functions to the presence of perineuronal nets which, notably, forecasted their role in disease development.…”

Section: The Phenotypic Appearance Of the Brain Extracellular Matrixmentioning

confidence: 99%

The Role of Extracellular Matrix in Human Neurodegenerative Diseases

Pintér

Alpár

2022

IJMS

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The dense neuropil of the central nervous system leaves only limited space for extracellular substances free. The advent of immunohistochemistry, soon followed by advanced diagnostic tools, enabled us to explore the biochemical heterogeneity and compartmentalization of the brain extracellular matrix in exploratory and clinical research alike. The composition of the extracellular matrix is critical to shape neuronal function; changes in its assembly trigger or reflect brain/spinal cord malfunction. In this study, we focus on extracellular matrix changes in neurodegenerative disorders. We summarize its phenotypic appearance and biochemical characteristics, as well as the major enzymes which regulate and remodel matrix establishment in disease. The specifically built basement membrane of the central nervous system, perineuronal nets and perisynaptic axonal coats can protect neurons from toxic agents, and biochemical analysis revealed how the individual glycosaminoglycan and proteoglycan components interact with these molecules. Depending on the site, type and progress of the disease, select matrix components can either proactively trigger the formation of disease-specific harmful products, or reactively accumulate, likely to reduce tissue breakdown and neuronal loss. We review the diagnostic use and the increasing importance of medical screening of extracellular matrix components, especially enzymes, which informs us about disease status and, better yet, allows us to forecast illness.

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Role of the Extracellular Matrix in Alzheimer’s Disease

Cited by 67 publications

References 135 publications

An Alzheimer’s disease patient-derived olfactory cell model identifies gene expression changes associated with cognition

An Alzheimer’s disease patient-derived olfactory cell model identifies gene expression changes associated with cognition

An Alzheimer’s Disease Patient-Derived Olfactory Stem Cell Model Identifies Gene Expression Changes Associated with Cognition

The Role of Extracellular Matrix in Human Neurodegenerative Diseases

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