scholarly journals Disturbance of phylogenetic layer-specific adaptation of human brain gene expression in Alzheimer's disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Natasha Andressa Nogueira Jorge ◽  
Uwe Ueberham ◽  
Mara Knobloch ◽  
Peter F. Stadler ◽  
Jörg Fallmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Neurodegenerative Disorder ◽  
Critical Role ◽  
Subcortical White Matter ◽  
Specific Gene ◽  
Specific Adaptation ◽  
Vesicle Exocytosis

AbstractAlzheimer's disease (AD) is a progressive neurodegenerative disorder with typical neuropathological hallmarks, such as neuritic plaques and neurofibrillary tangles, preferentially found at layers III and V. The distribution of both hallmarks provides the basis for the staging of AD, following a hierarchical pattern throughout the cerebral cortex. To unravel the background of this layer-specific vulnerability, we evaluated differential gene expression of supragranular and infragranular layers and subcortical white matter in both healthy controls and AD patients. We identified AD-associated layer-specific differences involving protein-coding and non-coding sequences, most of those present in the subcortical white matter, thus indicating a critical role for long axons and oligodendrocytes in AD pathomechanism. In addition, GO analysis identified networks containing synaptic vesicle transport, vesicle exocytosis and regulation of neurotransmitter levels. Numerous AD-associated layer-specifically expressed genes were previously reported to undergo layer-specific switches in recent hominid brain evolution between layers V and III, i.e., those layers that are most vulnerable to AD pathology. Against the background of our previous finding of accelerated evolution of AD-specific gene expression, here we suggest a critical role in AD pathomechanism for this phylogenetic layer-specific adaptation of gene expression, which is most prominently seen in the white matter compartment.

scholarly journals PET imaging of 18F-florbetapir in cognitively impaired individuals: Lack of activity within the cerebellar cortex

2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Michael A. Meyer ◽  
Allison Caccia ◽  
Danielle Martinez ◽  
Mark A. Mingos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Cerebellar Cortex ◽  
Pet Imaging ◽  
Parent Compound ◽  
Hepatic Metabolism ◽  
Subcortical White Matter ◽  
Clinical Value ◽  
Type Pattern

Ten individuals suspected of having possible Alzheimer disease underwent PET imaging using 18F-Flubetapir. Only one of ten individuals had a pattern typical for normal elderly control subjects with 9 of the 10 showing a Alzheimer type pattern for the cerebral cortex yet all 10 subjects had uniformly low to absent tracer localization to the cerebellar cortex; significantly high tracer activity was noted within the subcortical white matter of the cerebellum in a symmetric manner in all cases. In consideration of studies that have shown amyloid deposits within the cerebellar cortex in 90% of pathologically proven cases of Alzheimer’s disease, these findings raise questions about the actual clinical value of florbetapir PET imaging in evaluating cerebellar involvement and raises questions whether PET imaging of this tracer accurately portrays patterns of amyloid deposition, as there is rapid hepatic metabolism of the parent compound after intravenous injection. Possible links to Alzheimer’s disease related alterations in blood-brain barrier permeability to the parent compound and subsequent radiolabelled metabolites are discussed as potential mechanisms that could explain the associated localization of the tracer to the brainstem and subcortical white matter within the cerebrum and cerebellum of Alzheimer’s disease patients.

scholarly journals Integrated DNA methylation and gene expression profiling across multiple brain regions implicate novel genes in Alzheimer’s disease

2018 ◽  
Author(s):  
Stephen A. Semick ◽  
Rahul A. Bharadwaj ◽  
Leonardo Collado-Torres ◽  
Ran Tao ◽  
Joo Heon Shin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Brain Regions ◽  
Epigenetic Mechanism ◽  
Novel Genes ◽  
Age Related

AbstractBackgroundLate-onset Alzheimer’s disease (AD) is a complex age-related neurodegenerative disorder that likely involves epigenetic factors. To better understand the epigenetic state associated with AD represented as variation in DNA methylation (DNAm), we surveyed 420,852 DNAm sites from neurotypical controls (N=49) and late-onset AD patients (N=24) across four brain regions (hippocampus, entorhinal cortex, dorsolateral prefrontal cortex and cerebellum).ResultsWe identified 858 sites with robust differential methylation, collectively annotated to 772 possible genes (FDR<5%, within 10kb). These sites were overrepresented in AD genetic risk loci (p=0.00655), and nearby genes were enriched for processes related to cell-adhesion, immunity, and calcium homeostasis (FDR<5%). We analyzed corresponding RNA-seq data to prioritize 130 genes within 10kb of the differentially methylated sites, which were differentially expressed and had expression levels associated with nearby DNAm levels (p<0.05). This validated gene set includes previously reported (e.g. ANK1, DUSP22) and novel genes involved in Alzheimer’s disease, such as ANKRD30B.ConclusionsThese results highlight DNAm changes in Alzheimer’s disease that have gene expression correlates, implicating DNAm as an epigenetic mechanism underlying pathological molecular changes associated with AD. Furthermore, our framework illustrates the value of integrating epigenetic and transcriptomic data for understanding complex disease.

scholarly journals Effects of Swimming Training and Royal Jelly on BDNF and NGF Gene Expression in Hippocampus Tissue of Rats with Alzheimer’s Disease

2020 ◽  
Vol 22 (2) ◽  
Author(s):  
Amin Dehbozorgi ◽  
Laleh Behbudi Tabrizi ◽  
Seyed Ali Hosseini ◽  
Masod Haj Rasoli
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Royal Jelly ◽  
Neurodegenerative Disorder ◽  
Control Group ◽  
Swimming Training ◽  
Age Related ◽  
And Training ◽  
Ngf Gene

Background: Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. Evidence from neuropathological studies indicates that the levels of neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are compromised in AD. Objectives: The present study aimed to review the effects of swimming training and royal jelly (RJ) on BDNF and NGF gene expression in the hippocampus tissue of rats with AD. Methods: In the present experimental study, 25 rats with AD were divided into five groups, including (1) control, (2) sham, (3) RJ, (4) training, and (5) training with RJ. Five healthy rats were selected as the healthy control group to examine the effect of AD induction by 8 mg/kg trimethyltin chloride (TMT) intra-peritoneally on BDNF and NGF. During eight weeks, groups 3 and 5 received 100 mg/kg RJ daily intra-peritoneally, and groups 4 and 5 swam in a rat swimming tank three sessions per week. One-way ANOVA with Tukey’s post hoc test was used for data analysis in SPSS 20 software (P < 0.05). Results: The induction of AD by TMT had a significant effect on the reduction of BDNF (P = 0.001) and NGF (P = 0.001). However, RJ had a significant effect on the increase of NGF (P = 0.03). Nevertheless, RJ (P = 0.99), training (P = 0.99), and training with RJ (P = 0.94) had no significant effect on BDNF and training (P = 0.99) and training with RJ (P = 0.97) had no significant effect on NGF. Conclusions: It appears that RJ has a significant effect on the increase of NGF gene expression in the hippocampus tissue of rats with AD. Nevertheless, RJ consumption simultaneously with swimming training has no significant effect on BDNF and NGF.

scholarly journals Zinc transporters in Alzheimer’s disease

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingshuo Xu ◽  
Guiran Xiao ◽  
Li Liu ◽  
Minglin Lang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Critical Role ◽  
Zinc Transporters ◽  
Protein Levels ◽  
Zinc Chelator ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies

AbstractAlzheimer’s disease (AD) is the most devastating neurodegenerative disorder. Due to the increase in population and longevity, incidence will triple by the middle of the twenty-first century. So far, no treatment has prevented or reversed the disease. More than 20 years of multidisciplinary studies have shown that brain zinc dyshomeostasis may play a critical role in AD progression, which provides encouraging clues for metal-targeted therapies in the treatment of AD. Unfortunately, the pilot clinical application of zinc chelator and/or ionophore strategy, such as the use of quinoline-based compounds, namely clioquinol and PBT2, has not yet been successful. The emerging findings revealed a list of key zinc transporters whose mRNA or protein levels were abnormally altered at different stages of AD brains. Furthermore, specifically modulating the expression of some of the zinc transporters in the central nervous system through genetic methods slowed down or prevented AD progression in animal models, resulting in significantly improved cognitive performance, movement, and prolonged lifespan. Although the underlying molecular mechanisms are not yet fully understood, it shed new light on the treatment or prevention of the disease. This review considers recent advances regarding AD, zinc and zinc transporters, recapitulating their relationships in extending our current understanding of the disease amelioration effects of zinc transport proteins as potential therapeutic targets to cure AD, and it may also provide new insights to identify novel therapeutic strategies for ageing and other neurodegenerative diseases, such as Huntington’s and Parkinson’s disease.

Axon–glial disruption: the link between vascular disease and Alzheimer's disease?

2011 ◽  
Vol 39 (4) ◽  
pp. 881-885 ◽  
Author(s):  
Karen Horsburgh ◽  
Michell M. Reimer ◽  
Philip Holland ◽  
Guiquan Chen ◽  
Gillian Scullion ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Cognitive Decline ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Early Event ◽  
Published Data

Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

Alzheimer's disease (AD) : AT8 recognizes degenerating ectopic neurons and astrocytes in the subcortical white matter.

2005 ◽  
Vol 161 (3) ◽  
pp. 338-339
Author(s):  
O. Bugiani ◽  
G. Giaccone ◽  
R. Capobianco ◽  
F. Tagliavini ◽  
B. Ghetti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Subcortical White Matter ◽  
Ectopic Neurons
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