Neuropathology

2013 ◽  
Author(s):  
Johannes Attems ◽  
Kurt A. Jellinger
Keyword(s):  
Prion Diseases ◽  
Hippocampal Sclerosis ◽  
Neurofibrillary Tangle ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
Corticobasal Degeneration ◽  
Amyloid Angiopathy ◽  
Argyrophilic Grain Disease ◽  
Argyrophilic Grain ◽  
Cerebral Amyloid

This chapter describes the main neuropathological features of the most common age associated neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies as well as other less frequent ones such as multiple system atrophy, Pick's disease, corticobasal degeneration, progressive supranuclear palsy, argyrophilic grain disease, neurofibrillary tangle dominant dementia, frontotemporal lobar degeneration with TDP-43 pathology and Huntington's disease. Likewise cerebral amyloid angiopathy, hippocampal sclerosis, vascular dementia and prion diseases are described. A main aim of this chapter is to assist the reader in interpreting neuropathological reports, hence criteria for the neuropathological classifications of the major diseases are provided. One section covers general considerations on neurodegeneration and basic pathophysiological mechanisms of tau, amyloid-β, α-synuclein, TDP-43 and prions are briefly described in the sections on the respective diseases. Finally, one section is dedicated to cerebral multimorbidity and we give a view on currently emerging neuropathological methods.

Neuropathology

2020 ◽  
pp. 77-98
Author(s):  
Johannes Attems ◽  
Kurt A. Jellinger
Keyword(s):  
Frontotemporal Lobar Degeneration ◽  
Dementia With Lewy Bodies ◽  
Prion Diseases ◽  
Hippocampal Sclerosis ◽  
Neurofibrillary Tangle ◽  
Lewy Bodies ◽  
Corticobasal Degeneration ◽  
Amyloid Angiopathy ◽  
Argyrophilic Grain ◽  
Cerebral Amyloid

This chapter describes the main neuropathological features of the most common age-associated neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and dementia with Lewy bodies, as well as other less frequent ones such as multiple system atrophy, Pick’s disease, corticobasal degeneration, progressive supranuclear palsy, argyrophilic grain disease, neurofibrillary tangle-dominant dementia, frontotemporal lobar degeneration with TDP-43 pathology, and Huntington’s disease. Likewise, cerebral amyloid angiopathy, hippocampal sclerosis, vascular dementia, and prion diseases are described. A main aim of this chapter is to assist the reader in interpreting neuropathological reports; hence criteria for the neuropathological classifications of the major diseases are provided. One section covers general considerations on neurodegeneration, and basic pathophysiological mechanisms of tau, amyloid-β‎, α‎-synuclein, TDP-43, and prions are briefly described in the sections on the respective diseases. Finally, one section is dedicated to cerebral multimorbidity, and a view on currently emerging neuropathological methods is given.

scholarly journals Cerebral amyloid angiopathy and comparative analysis of amyloid-β protein in birds

2018 ◽  
Author(s):  
Yumi Une ◽  
Mutsumi Yamazaki ◽  
Maho Morimoto ◽  
Fuyuki Kametani ◽  
Dennilyn Parker ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Cerebral Amyloid Angiopathy ◽  
Senile Plaques ◽  
Neurofibrillary Tangle ◽  
Bird Species ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Amyloid Β Protein ◽  
Cerebral Amyloid

Senile plaques and cerebral amyloid angiopathy (CAA)?are well-documented in various mammals, and several species even exhibit neurofibrillary tangle (NFT). However, we know far less about whether such symptoms are present in birds. Therefore, here we clarified the occurrence and pathogenesis of avian aβ-related lesions, analyzing the aβ amino-acid sequence across 28 birds at multiple life stages, representing 15 species, 14 genera, and 9 nine families.?We also determined the expected aβ amino-acid sequence after comparing data from the brains of nine birds (seven species) with publicly available NCBI data. We observed CAA and senile plaque-like deposition only in a female Amazon parrot, estimated to be around 30–40 years old. We identified two Aβ depositions (40 and 42) in the same location that correspond to Aβ 6-42. Additionally, we observed severe Aβ deposition, accompanied by severe hemorrhaging, in blood vessels of the superficial and deep portions of the brain. These lesions were directly related to the cause of death. Of 40 bird species, 36 exhibited type 1 Aβ amino-acid sequences, similar to humans. Given that all of these birds were old, our results suggest that Aβ is deposited primarily as CAA as the animals age. This report is the first clinically based description of CAA in birds. Interspecific variation likely exists because we identified species that did not exhibit Aβ deposition even when the birds are old enough. However, even birds of the same taxonomic status differed in whether they possessed or lacked Aβ deposition. Thus, other factors besides Aβ amino-acid sequence could influence this symptom.

scholarly journals Cerebral amyloid angiopathy severity is linked to dilation of juxtacortical perivascular spaces

2015 ◽  
Vol 36 (3) ◽  
pp. 576-580 ◽  
Author(s):  
Susanne J van Veluw ◽  
Geert Jan Biessels ◽  
Willem H Bouvy ◽  
Wim GM Spliet ◽  
Jaco JM Zwanenburg ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Resonance Imaging ◽  
Centrum Semiovale ◽  
Tissue Sections ◽  
Cortical Areas ◽  
Cerebral Amyloid

Perivascular spaces are an emerging marker of small vessel disease. Perivascular spaces in the centrum semiovale have been associated with cerebral amyloid angiopathy. However, a direct topographical relationship between dilated perivascular spaces and cerebral amyloid angiopathy severity has not been established. We examined this association using post-mortem magnetic resonance imaging in five cases with evidence of cerebral amyloid angiopathy pathology. Juxtacortical perivascular spaces dilation was evaluated on T2 images and related to cerebral amyloid angiopathy severity in overlying cortical areas on 34 tissue sections stained for Amyloid β. Degree of perivascular spaces dilation was significantly associated with cerebral amyloid angiopathy severity (odds ratio = 3.3, 95% confidence interval 1.3–7.9, p = 0.011). Thus, dilated juxtacortical perivascular spaces are a promising neuroimaging marker of cerebral amyloid angiopathy severity.

scholarly journals A Simplified Brain Blocking Protocol Optimized for the Diagnosis of Neurodegenerative Disease Saves Time and Money While Preserving Anatomic Relationships

2020 ◽  
Author(s):  
Nathan F. Clement ◽  
John C. DeWitt ◽  
Matthew P. Frosch ◽  
Maria Martinez-Lage ◽  
Wesley R. Samore ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Alzheimer Disease ◽  
Neurodegenerative Disease ◽  
Corticobasal Degeneration ◽  
Amyloid Angiopathy ◽  
Standard Protocol ◽  
Lewy Pathology ◽  
Disease Research ◽  
Sampling Protocols ◽  
Cerebral Amyloid

Context.— Postmortem evaluation for neurodegenerative disease is expensive in time and materials. These challenges can be met by implementing simpler sampling protocols while preserving anatomic relations. Objective.— To determine the diagnostic effectiveness and cost-effectiveness of a simplified brain blocking protocol compared with the standard blocking protocol used in our Alzheimer disease research center (ADRC). Design.— We prospectively compared the neuropathologic diagnoses established from our standard 19-cassette/19 brain sites ADRC protocol to a simplified 6-cassette/12 brain sites protocol in 52 consecutive cases. The simplified protocol generated 14 slides for comparison to 52 slides from our standard protocol. Results.— Compared with the ADRC protocol the simplified protocol produced Alzheimer Disease Neuropathologic Changes probability scores that were the same in 50 of 52 cases (r = 0.99). Staging for Lewy pathology was equivalent in 45 of 52 (r = 0.98), scoring for cerebral amyloid angiopathy was equivalent in 48 of 52 (r = 0.97), and grading for arteriolosclerosis was the same in 45 of 52 cases (r = 0.92). Progressive supranuclear palsy (n = 4), multiple system atrophy (n = 2), and corticobasal degeneration (n = 1) could be diagnosed by either protocol independently. The estimated savings per case was 72% or $1744.89 ($2436.37 [ADRC] versus $691.48 [simplified]). Conclusions.— The diagnosis of neurodegenerative disease at autopsy can be done accurately with a less expensive, simplified protocol. Our protocol is similar to those of previously published approaches, but it has a simpler organization scheme. This method should be valuable to institutions where autopsy cost considerations may be important.

scholarly journals Evidence of amyloid-β cerebral amyloid angiopathy transmission through neurosurgery

2018 ◽  
Vol 135 (5) ◽  
pp. 671-679 ◽  
Author(s):  
Zane Jaunmuktane ◽  
Annelies Quaegebeur ◽  
Ricardo Taipa ◽  
Miguel Viana-Baptista ◽  
Raquel Barbosa ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

Amyloid-β disrupts unitary calcium entry through endothelial NMDA receptors in mouse cerebral arteries

2021 ◽  
pp. 0271678X2110395
Author(s):  
Emily C Peters ◽  
Michael T Gee ◽  
Lukas N Pawlowski ◽  
Allison M Kath ◽  
Felipe D Polk ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cerebral Arteries ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Wild Type ◽  
Pial Arteries ◽  
Aspartate Receptor ◽  
Model Of Alzheimer’S Disease ◽  
Intracellular Ca ◽  
Cerebral Amyloid

Transient increases in intracellular Ca2+ activate endothelium-dependent vasodilatory pathways. This process is impaired in cerebral amyloid angiopathy, where amyloid- β(1-40) accumulates around blood vessels. In neurons, amyloid- β impairs the Ca2+-permeable N-methyl-D-aspartate receptor (NMDAR), a mediator of endothelium-dependent dilation in arteries. We hypothesized that amyloid- β(1-40) reduces NMDAR-elicited Ca2+ signals in mouse cerebral artery endothelial cells, blunting dilation. Cerebral arteries isolated from 4-5 months-old, male and female cdh5:Gcamp8 mice were used for imaging of unitary Ca2+ influx through NMDAR ( NMDAR sparklets) and intracellular Ca2+ transients. The NMDAR agonist NMDA (10 µmol/L) increased frequency of NMDAR sparklets and intracellular Ca2+ transients in endothelial cells; these effects were prevented by NMDAR antagonists D-AP5 and MK-801. Next, we tested if amyloid- β(1-40) impairs NMDAR-elicited Ca2+ transients. Cerebral arteries incubated with amyloid- β(1-40) (5 µmol/L) exhibited reduced NMDAR sparklets and intracellular Ca2+ transients. Lastly, we observed that NMDA-induced dilation of pial arteries is reduced by acute intraluminal amyloid- β(1-40), as well as in a mouse model of Alzheimer’s disease, the 5x-FAD, linked to downregulation of Grin1 mRNA compared to wild-type littermates. These data suggest that endothelial NMDAR mediate dilation via Ca2+-dependent pathways, a process disrupted by amyloid- β(1-40) and impaired in 5x-FAD mice.

Vessels Sing Their ARIAs: The Role of Vascular Amyloid in the Age of Aducanumab

Stroke ◽  
2021 ◽  
Author(s):  
Lukas Sveikata ◽  
Andreas Charidimou ◽  
Anand Viswanathan
Keyword(s):  
Clinical Trials ◽  
Alzheimer Disease ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Β ◽  
High Rate ◽  
Amyloid Angiopathy ◽  
Cerebrovascular Pathology ◽  
Cerebral Amyloid

We review the implications of the recently approved aducanumab amyloid-β immunotherapy for treating Alzheimer disease with comorbid cerebral amyloid angiopathy. In clinical trials, amyloid-β immunotherapy has been associated with a high rate of amyloid-related imaging abnormalities, potentially driven by coexisting cerebral amyloid angiopathy. Therefore, immunotherapy’s efficacy in patients may be modified by coexisting cerebrovascular pathology. We discuss the contributions of cerebral amyloid angiopathy on the development of amyloid-related imaging abnormalities and propose strategies to identify cerebral amyloid angiopathy in patients considered for immunotherapy.

scholarly journals Neuropathologic burden and the degree of frailty in relation to global cognition and dementia

Neurology ◽  
2020 ◽  
Vol 95 (24) ◽  
pp. e3269-e3279
Author(s):  
Lindsay M.K. Wallace ◽  
Olga Theou ◽  
Sultan Darvesh ◽  
David A. Bennett ◽  
Aron S. Buchman ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Hippocampal Sclerosis ◽  
Frailty Index ◽  
Secondary Analysis ◽  
Lewy Bodies ◽  
Clinical Syndrome ◽  
Future Research ◽  
Amyloid Angiopathy ◽  
Integrative View ◽  
Global Cognition

ObjectiveTo test the hypothesis that degree of frailty and neuropathologic burden independently contribute to global cognition and odds of dementia.MethodsThis was a secondary analysis of a prospective cohort study of older adults living in Illinois. Participants underwent an annual neuropsychological and clinical evaluation. We included 625 participants (mean age 89.7 ± 6.1 years; 67.5% female) who died and underwent autopsy. We quantified neuropathology using an index measure of 10 neuropathologic features: β-amyloid deposition, hippocampal sclerosis, Lewy bodies, tangle density, TDP-43, cerebral amyloid angiopathy, arteriolosclerosis, atherosclerosis, and gross and chronic cerebral infarcts. Clinical consensus determined dementia status, which we coded as no cognitive impairment, mild cognitive impairment, or dementia. A battery of 19 tests spanning multiple domains quantified global cognition. We operationalized frailty using a 41-item frailty index. We employed regression analyses to model relationships between neuropathology, frailty, and dementia.ResultsBoth frailty and a neuropathology index were independently associated with global cognition and dementia status. These results held after controlling for traditional pathologic measures in a sample of participants with Alzheimer clinical syndrome. Frailty improved the fit of the model for dementia status (χ2[2] 72.64; p < 0.0001) and explained an additional 11%–12% of the variance in the outcomes.ConclusionDementia is a multiply determined condition, to which both general health, as captured by frailty, and neuropathology significantly contribute. This integrative view of dementia and health has implications for prevention and therapy; specifically, future research should evaluate frailty as a means of dementia risk reduction.

Sign in / Sign up

Export Citation Format

Share Document