scholarly journals Amyloid-β Peptide and Oligomers in the Brain and Cerebrospinal Fluid of Aged Canines

2010 ◽  
Vol 20 (2) ◽  
pp. 637-646 ◽  
Author(s):  
Elizabeth Head ◽  
Viorela Pop ◽  
Floyd Sarsoza ◽  
Rakez Kayed ◽  
Tina L. Beckett ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
The Brain

scholarly journals Shear-Induced Amyloid Aggregation in the Brain: V. Are Alzheimer’s and Other Amyloid Diseases Initiated in the Lower Brain and Brainstem by Cerebrospinal Fluid Flow Stresses?

2020 ◽  
pp. 1-24
Author(s):  
Conrad N. Trumbore
Keyword(s):  
Cerebrospinal Fluid ◽  
Conformational Changes ◽  
Extensional Flow ◽  
Amyloid Β ◽  
High Energy ◽  
Mechanical Agitation ◽  
Cerebrospinal Fluid Flow ◽  
Pulse Waves ◽  
Amyloid Diseases ◽  
The Brain

Amyloid-β (Aβ) and tau oligomers have been identified as neurotoxic agents responsible for causing Alzheimer’s disease (AD). Clinical trials using Aβ and tau as targets have failed, giving rise to calls for new research approaches to combat AD. This paper provides such an approach. Most basic AD research has involved quiescent Aβ and tau solutions. However, studies involving laminar and extensional flow of proteins have demonstrated that mechanical agitation of proteins induces or accelerates protein aggregation. Recent MRI brain studies have revealed high energy, chaotic motion of cerebrospinal fluid (CSF) in lower brain and brainstem regions. These and studies showing CSF flow within the brain have shown that there are two energetic hot spots. These are within the third and fourth brain ventricles and in the neighborhood of the circle of Willis blood vessel region. These two regions are also the same locations as those of the earliest Aβ and tau AD pathology. In this paper, it is proposed that cardiac systolic pulse waves that emanate from the major brain arteries in the lower brain and brainstem regions and whose pulse waves drive CSF flows within the brain are responsible for initiating AD and possibly other amyloid diseases. It is further proposed that the triggering of these diseases comes about because of the strengthening of systolic pulses due to major artery hardening that generates intense CSF extensional flow stress. Such stress provides the activation energy needed to induce conformational changes of both Aβ and tau within the lower brain and brainstem region, producing unique neurotoxic oligomer molecule conformations that induce AD.

scholarly journals Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shorena Janelidze ◽  
Erik Stomrud ◽  
Ruben Smith ◽  
Sebastian Palmqvist ◽  
Niklas Mattsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Pet Tracer ◽  
Positron Emission ◽  
Diagnostic Work ◽  
Work Up ◽  
The Brain ◽  
Better Than

AbstractCerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.

scholarly journals Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer’s disease

2019 ◽  
Vol 11 (507) ◽  
pp. eaav6221 ◽  
Author(s):  
Michael Ewers ◽  
Nicolai Franzmeier ◽  
Marc Suárez-Calvet ◽  
Estrella Morenas-Rodriguez ◽  
Miguel Angel Araque Caballero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Elderly Subjects ◽  
Amyloid Β Peptide ◽  
Loss Of Function ◽  
Clinical Progression ◽  
Cognitively Normal ◽  
Soluble Trem2

Loss of function of TREM2, a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer’s disease (AD). We therefore examined whether soluble TREM2 (sTREM2) concentrations in cerebrospinal fluid (CSF) were associated with reduced rates of cognitive decline and clinical progression in subjects with AD or mild cognitive impairment (MCI). We measured sTREM2 in CSF samples from 385 elderly subjects, including cognitively normal controls, individuals with MCI, and subjects with AD dementia (follow-up period: mean, 4 years; range 1.5 to 11.5 years). In subjects with AD defined by evidence of CSF Aβ1–42 (amyloid β-peptide 1 to 42; A+) and CSF p-tau181 (tau phosphorylated on amino acid residue 181; T+), higher sTREM2 concentrations in CSF at baseline were associated with attenuated decline in memory and cognition. When analyzed in clinical subgroups, an association between higher CSF sTREM2 concentrations and subsequent reduced memory decline was consistently observed in individuals with MCI or AD dementia, who were positive for CSF Aβ1–42 and CSF p-tau181 (A+T+). Regarding clinical progression, a higher ratio of CSF sTREM2 to CSF p-tau181 concentrations predicted slower conversion from cognitively normal to symptomatic stages or from MCI to AD dementia in the subjects who were positive for CSF Aβ1–42 and CSF p-tau181. These results suggest that sTREM2 is associated with attenuated cognitive and clinical decline, a finding with important implications for future clinical trials targeting the innate immune response in AD.

Phosphorylation of a full length amyloid-β peptide modulates its amyloid aggregation, cell binding and neurotoxic properties

2017 ◽  
Vol 13 (8) ◽  
pp. 1545-1551 ◽  
Author(s):  
Elaheh Jamasbi ◽  
Frances Separovic ◽  
Mohammed Akhter Hossain ◽  
Giuseppe Donato Ciccotosto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
Full Length ◽  
Amyloid Β Peptide ◽  
Amyloid Aggregation ◽  
Cell Binding ◽  
The Brain

Phosphorylation of Aβ42 promotes the formation of amyloid plaques in the brain, which lack the neurotoxic properties associated with oligomeric species causing pathogenesis in Alzheimer's disease.

scholarly journals The pro-neurotrophin receptor sortilin is a major neuronal APOE receptor for catabolism of amyloid-β peptide in the brain

2013 ◽  
Vol 8 (S1) ◽  
Author(s):  
Anne-Sophie Carlo ◽  
Camilla Gustafsen ◽  
Guido Mastrobuoni ◽  
Morten Nielsen ◽  
Stefan Kempa ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Neurotrophin Receptor ◽  
Amyloid Β Peptide ◽  
Apoe Receptor ◽  
The Brain

scholarly journals Fluid dynamics of cerebrospinal fluid flow in perivascular spaces

2019 ◽  
Vol 16 (159) ◽  
pp. 20190572 ◽  
Author(s):  
John H. Thomas
Keyword(s):  
Fluid Dynamics ◽  
Cerebrospinal Fluid ◽  
Dynamic Models ◽  
Fluid Dynamic ◽  
Critical Evaluation ◽  
Amyloid Β ◽  
Perivascular Spaces ◽  
Waste Products ◽  
Basic Fluid ◽  
The Brain

The flow of cerebrospinal fluid along perivascular spaces (PVSs) is an important part of the brain’s system for delivering nutrients and eliminating metabolic waste products (such as amyloid-β); it also offers a pathway for the delivery of therapeutic drugs to the brain parenchyma. Recent experimental results have resolved several important questions about this flow, setting the stage for advances in our understanding of its fluid dynamics. This review summarizes the new experimental evidence and provides a critical evaluation of previous fluid-dynamic models of flows in PVSs. The review also discusses some basic fluid-dynamic concepts relevant to these flows, including the combined effects of diffusion and advection in clearing solutes from the brain.

scholarly journals Accumulation of Alzheimer Amyloid-β Peptide in Cultured Myocytes is Enhanced by Serum and Reduced by Cerebrospinal Fluid

1997 ◽  
Vol 56 (3) ◽  
pp. 263-272 ◽  
Author(s):  
BOZENA MAZUR-KOLECKA ◽  
JANUSZ FRACKOWIAK ◽  
RICHARD T. CARROLL ◽  
HENRYK M. WISNIEWSKI
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Amyloid Β Peptide

In Vivo Microdialysis in Mice Captures Changes in Alzheimer’s Disease Cerebrospinal Fluid Biomarkers Consistent with Developing Pathology

2021 ◽  
pp. 1-14
Author(s):  
Christiana Bjorkli ◽  
Claire Louet ◽  
Trude Helen Flo ◽  
Mary Hemler ◽  
Axel Sandvig ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Mouse Model ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Intracerebral Microdialysis ◽  
Preclinical Models ◽  
The Brain

Background: Preclinical models of Alzheimer’s disease (AD) can provide valuable insights into the onset and progression of the disease, such as changes in concentrations of amyloid-β (Aβ) and tau in cerebrospinal fluid (CSF). However, such models are currently underutilized due to limited advancement in techniques that allow for longitudinal CSF monitoring. Objective: An elegant way to understand the biochemical environment in the diseased brain is intracerebral microdialysis, a method that has until now been limited to short-term observations, or snapshots, of the brain microenvironment. Here we draw upon patient-based findings to characterize CSF biomarkers in a commonly used preclinical mouse model for AD. Methods: Our modified push-pull microdialysis method was first validated ex vivo with human CSF samples, and then in vivo in an AD mouse model, permitting assessment of dynamic changes of CSF Aβ and tau and allowing for better translational understanding of CSF biomarkers. Results: We demonstrate that CSF biomarker changes in preclinical models capture what is observed in the brain; with a decrease in CSF Aβ observed when plaques are deposited, and an increase in CSF tau once tau pathology is present in the brain parenchyma. We found that a high molecular weight cut-off membrane allowed for simultaneous sampling of Aβ and tau, comparable to CSF collection by lumbar puncture in patients. Conclusion: Our approach can further advance AD and other neurodegenerative research by following evolving neuropathology along the disease cascade via consecutive sampling from the same animal and can additionally be used to administer pharmaceutical compounds and assess their efficacy (Bjorkli, unpublished data).

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