Beta Amyloid Peptide: Research Paper : Aβ (Amyloid Beta) and Tau Tangle Pathology Modifies the Association Between Small Vessel Disease and Cortical Microinfarcts

Aβ (Amyloid Beta) and Tau Tangle Pathology Modifies the Association Between Small Vessel Disease and Cortical Microinfarcts

Abstract

Background and purpose: There is increasing recognition of the importance of cortical microinfarcts to overall brain health, cognition, and Alzheimer dementia. Cerebral small vessel pathologies are associated with microinfarcts and frequently coexist with Alzheimer disease; however, the extent to which Aβ (amyloid beta) and tau pathology modulates microvascular pathogenesis is not fully understood. Study objective was to examine the relationship of small vessel pathologies, arteriolosclerosis, and cerebral amyloid angiopathy, with cortical microinfarcts in people with differing levels of Aβ or tau tangle burden.

Methods: Participants were 1489 autopsied older people (mean age at death, 89 years; 67% women) from 1 of 3 ongoing clinical-pathological cohort studies of aging. Neuropathological evaluation identified cortical Aβ and tau tangle burden using immunohistochemistry in 8 brain regions, provided semiquantitative grading of cerebral vessel pathologies, and identified the presence of cortical microinfarcts. Logistic regression models adjusted for demographics and atherosclerosis and examined whether Aβ or tau tangle burden modified relations between small vessel pathologies and cortical microinfarcts.

Results: Cortical microinfarcts were present in 17% of older people, moderate-to-severe cerebral amyloid angiopathy pathology in 36%, and arteriolosclerosis in 34%. In logistic regression models, we found interactions with Aβ and tau tangles, reflecting that the association between arteriolosclerosis and cortical microinfarcts was stronger in the context of greater Aβ (estimate, 0.15; SE=0.07; P=0.02) and tau tangle burden (estimate, 0.13; SE=0.06; P=0.02). Interactions also emerged for cerebral amyloid angiopathy, suggesting that the association between cerebral amyloid angiopathy and cortical microinfarcts is more robust in the presence of higher Aβ (estimate, 0.27; SE=0.07; P<0.001) and tangle burden (estimate, 0.16; SE=0.06; P=0.005).

Conclusions: These findings suggest that in the presence of elevated Aβ or tangle pathology, small vessel pathologies are associated with greater microvascular tissue injury, highlighting a potential link between neurodegenerative and vascular mechanisms.

Keywords: Alzheimer disease; arteriolosclerosis; atherosclerosis; logistic models; longitudinal studies.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33567873/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Hypermethylation of Mitochondrial Cytochrome b and Cytochrome c Oxidase II Genes with Decreased Mitochondrial DNA Copy Numbers in the APP/PS1 Transgenic Mouse Model of Alzheimer's Disease

Hypermethylation of Mitochondrial Cytochrome b and Cytochrome c Oxidase II Genes with Decreased Mitochondrial DNA Copy Numbers in the APP/PS1 Transgenic Mouse Model of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is the most common cause of dementia. Increasing evidence shows that mitochondrial DNA (mtDNA) methylation plays an essential role in many diseases related to mitochondrial dysfunction. Since mitochondrial impairment is a key feature of AD, mtDNA methylation may also contribute to AD, but few studies have addressed this issue. Methylation changes of the mitochondrial cytochrome b (CYTB) and cytochrome c oxidase II (COX II) genes in AD have not been reported. We analyzed mtDNA methylation changes of the CYTB and COX II genes in an APP/PS1 transgenic mouse model of AD using pyrosequencing. We examined mtDNA copy numbers and the levels of expression by quantitative real-time PCR. Average methylation levels of different CpG sites were ≤ 4.0%. Methylated mtDNA accounted for only a small part of the total mtDNA. We also observed hypermethylation of mitochondrial CYTB and COX II genes with decreased mtDNA copy numbers and expression in the hippocampi of APP/PS1 transgenic mice. mtDNA methylation may play an important role in AD pathology, which may open a new window for AD therapy.

Keywords: Alzheimer's disease; Electron transport chain; Mitochondrial DNA methylation; Mitoepigenetics; Pyrosequencing.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33580369/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Advances in neuroimaging to support translational medicine in dementia

Advances in neuroimaging to support translational medicine in dementia

Abstract

Advances in neuroimaging are ideally placed to facilitate the translation from progress made in cellular genetics and molecular biology of neurodegeneration into improved diagnosis, prevention and treatment of dementia. New positron emission tomography (PET) ligands allow one to quantify neuropathology, inflammation and metabolism in vivo safely and reliably, to examine mechanisms of human disease and support clinical trials. Developments in MRI-based imaging and neurophysiology provide complementary quantitative assays of brain function and connectivity, for the direct testing of hypotheses of human pathophysiology. Advances in MRI are also improving the quantitative imaging of vascular risk and comorbidities. In combination with large datasets, open data and artificial intelligence analysis methods, new informatics-based approaches are set to enable accurate single-subject inferences for diagnosis, prediction and treatment that have the potential to deliver precision medicine for dementia. Here, we show, through the use of critically appraised worked examples, how neuroimaging can bridge the gaps between molecular biology, neural circuits and the dynamics of the core systems that underpin complex behaviours. We look beyond traditional structural imaging used routinely in clinical care, to include ultrahigh field MRI (7T MRI), magnetoencephalography and PET with novel ligands. We illustrate their potential as safe, robust and sufficiently scalable to be viable for experimental medicine studies and clinical trials. They are especially informative when combined in multimodal studies, with model-based analyses to test precisely defined hypotheses.

Keywords: MRI; PET; dementia; functional imaging; image analysis.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33568448/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : The role of immune-mediated alterations and disorders in ALS disease

The role of immune-mediated alterations and disorders in ALS disease

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that leads to neuronal death in the brain and spinal cord. Over the last decades, evidence has emerged regarding the functional diversity of astrocytes, microglia, and T cells in the central nervous system (CNS), and the role of neuroinflammation in ALS. In this review, we summarize current knowledge regarding neuroinflammation in ALS, both at the level of specific molecular pathways and potential cellular pathways as well as outline questions about the immune mechanisms involved in ALS pathogenesis.

Keywords: ALS; Autoimmunity; Glial cells; Neuroinflammation.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33583639/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Resting-state EEG alpha/theta ratio related to neuropsychological test performance in Parkinson's Disease

Resting-state EEG alpha/theta ratio related to neuropsychological test performance in Parkinson's Disease

Abstract

Objective: To determine possible associations of hemispheric-regional alpha/theta ratio (α/θ) with neuropsychological test performance in Parkinson's Disease (PD) non-demented patients.

Methods: 36 PD were matched to 36 Healthy Controls (HC). The α/θ in eight hemispheric regions was computed from the relative power spectral density of the resting-state quantitative electroencephalogram (qEEG). Correlations between α/θ and performance in several neuropsychological tests were conducted, significant findings were included in a moderation analysis.

Results: The α/θ in all regions was lower in PD than in HC, with larger effect sizes in the posterior regions. Right parietal, and right and left occipital α/θ had significant positive correlations with performance in Judgement of Line Orientation Test (JLOT) in PD. Adjusted moderation analysis indicated that right, but not left, occipital α/θ influenced the JLOT performance related to PD.

Conclusions: Reduction of the occipital α/θ, in particular on the right side, was associated with visuospatial performance impairment in PD.

Significance: Visuospatial impairment in PD, which is highly correlated with the subsequent development of dementia, is reflected in α/θ in the right posterior regions. The right occipital α/θ may represent a useful qEEG marker for evaluating the presence of early signs of cognitive decline in PD and the subsequent risk of dementia.

Keywords: Alpha rhythm; Electroencephalography; Neuropsychological tests; Parkinson's Disease; Theta rhythm.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33571883/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Chalcone and its analogs: Therapeutic and diagnostic applications in Alzheimer's disease

Chalcone and its analogs: Therapeutic and diagnostic applications in Alzheimer's disease

Abstract

Chalcone [(E)-1,3-diphenyl-2-propene-1-one], a small molecule with α, β unsaturated carbonyl group is a precursor or component of many natural flavonoids and isoflavonoids. It is one of the privileged structures in medicinal chemistry. It possesses a wide range of biological activities encouraging many medicinal chemists to study this scaffold for its usefulness to oncology, infectious diseases, virology and neurodegenerative diseases including Alzheimer's disease (AD). Small molecular size, convenient and cost-effective synthesis, and flexibility for modifications to modulate lipophilicity suitable for blood brain barrier (BBB) permeability make chalcones a preferred candidate for their therapeutic and diagnostic potential in AD. This review summarizes and highlights the importance of chalcone and its analogs as single target small therapeutic agents, multi-target directed ligands (MTDLs) as well as molecular imaging agents for AD. The information summarized here will guide many medicinal chemist and researchers involved in drug discovery to consider chalcone as a potential scaffold for the development of anti-AD agents including theranostics.

Keywords: Alzheimer's disease; Amyloid beta inhibition; Chalcone; Cholinesterase inhibitors; Molecular probes; Multi-target directed ligands; Neuroinflammation; Theranostic.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33571811/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Research Paper : Autonomic dysregulation as an early pathologic feature of Huntington Disease

Autonomic dysregulation as an early pathologic feature of Huntington Disease

Abstract

Objective: Autonomic nervous system (ANS) dysfunction has been described in adults with motor-manifest Huntington's Disease (HD) or those who are near their predicted motor onset. It is unclear if ANS dysfunction is present years prior to the onset of motor symptoms of HD. To bridge this gap in knowledge, we compared crude markers of ANS function between children with the gene-expansion that causes HD (GE group) who were decades from their predicted motor onset and gene-non-expanded children (GNE group).

Methods: We included participants from the Kids-HD study who were <18 years old. Linear mixed effects regression models were constructed that controlled for sex, age, and BMI, and included a random effect per participant and per family. We compared resting heart rate (rHR), core body temperature (CBT), systolic blood pressure (SBP), and diastolic blood pressure (DBP) between the GE (n = 84) and GNE (n = 238) groups. We then grouped participants from the GE group based on their predicted years to onset (YTO) and compared their vital signs to the GNE group.

Results: The GE group had higher rHR (∆ = 3.83, p = 0.0064), SBP (∆ = 2.38, p = 0.032), and CBT (∆ = 0.16, t = 2.92, p = 0.007). The mean rHR and CBT became significantly elevated compared to the GNE group in participants who had 15-25 YTO and those who had <15 YTO. The mean SBP of participants who had 25-35 YTO was significantly elevated compared to the GNE group.

Conclusion: ANS dysfunction in HD seems to occur approximately 20 years prior to the predicted onset of motor symptoms of HD.

Keywords: Autonomic nervous system; Blood pressure; Heart rate; Huntington Disease; Temperature.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33571915/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.