scholarly journals Mild Microglial Responses in the Cortex and Perivascular Macrophage Infiltration in Subcortical White Matter in Dogs with Age-Related Dementia Modelling Prodromal Alzheimer’s Disease

2021 ◽  
pp. 1-18
Author(s):  
Barbara Blicher Thomsen ◽  
Cecilie Madsen ◽  
Katrine Tækker Krohn ◽  
Camilla Thygesen ◽  
Trine Schütt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Subcortical White Matter ◽  
Cortical Layers ◽  
Rating Score ◽  
Perivascular Macrophage ◽  
Age Related ◽  
Prodromal Ad ◽  
Microglial Response

Background: Microglia contribute to Alzheimer’s disease (AD) pathogenesis by clearing amyloid-β (Aβ) and driving neuroinflammation. Domestic dogs with age-related dementia (canine cognitive dysfunction (CCD)) develop cerebral amyloidosis like humans developing AD, and studying such dogs can provide novel information about microglial response in prodromal AD. Objective: The aim was to investigate the microglial response in the cortical grey and the subcortical white matter in dogs with CCD versus age-matched cognitively normal dogs. Methods: Brains from aged dogs with CCD and age-matched controls without dementia were studied. Cases were defined by dementia rating score. Brain sections were stained for Aβ, thioflavin S, hyperphosphorylated tau, and the microglial-macrophage ionized calcium binding adaptor molecule 1 (Iba1). Results were correlated to dementia rating score and tissue levels of Aβ. Results: Microglial numbers were higher in the Aβ plaque-loaded deep cortical layers in CCD versus control dogs, while the coverage by microglial processes were comparable. Aβ plaques were of the diffuse type and without microglial aggregation. However, a correlation was found between the %Iba1 area and insoluble Aβ 42 and N-terminal pyroglutamate modified Aβ(N3pE)-42. The %Iba1 area was higher in white matter, showing phosphorylation of S396 tau, versus grey matter. Perivascular macrophage infiltrates were abundant in the white matter particularly in CDD dogs. Conclusion: The results from this study of the microglial-macrophage response in dogs with CCD are suggestive of relatively mild microglial responses in the Aβ plaque-loaded deep cortical layers and perivascular macrophage infiltrates in the subcortical white matter, in prodromal AD.

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.

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

Alzheimer’s Disease Genetics: A Dampened Microglial Response?

2021 ◽  
pp. 107385842110245
Author(s):  
Zena K. Chatila ◽  
Elizabeth M. Bradshaw
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immune ◽  
Regulatory Mechanisms ◽  
Innate Immune Cells ◽  
Genetic Studies ◽  
Age Related ◽  
Microglial Phenotype ◽  
The Central Nervous System ◽  
Microglial Response

Alzheimer’s disease (AD) is a debilitating age-related neurodegenerative condition. Unbiased genetic studies have implicated a central role for microglia, the resident innate immune cells of the central nervous system, in AD pathogenesis. On-going efforts are clarifying the biology underlying these associations and the microglial pathways that are dysfunctional in AD. Several genetic risk factors converge to decrease the function of activating microglial receptors and increase the function of inhibitory receptors, resulting in a seemingly dampened microglial phenotype in AD. Moreover, many of these microglial proteins that are genetically associated with AD appear to interact and share pathways or regulatory mechanisms, presenting several points of convergence that may be strategic targets for therapeutic intervention. Here, we review some of these studies and their implications for microglial participation in AD pathogenesis.

scholarly journals CSF in Epileptic Prodromal Alzheimer's Disease: No Diagnostic Contribution but a Pathophysiological One

2021 ◽  
Vol 12 ◽  
Author(s):  
Benjamin Cretin ◽  
Olivier Bousiges ◽  
Geoffroy Hautecloque ◽  
Nathalie Philippi ◽  
Frederic Blanc ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Surrogate Marker ◽  
Brain Magnetic Resonance Imaging ◽  
Csf Biomarkers ◽  
Epileptiform Discharges ◽  
Prodromal Ad ◽  
Prodromal Alzheimer’S Disease

Objective: To study whether cerebrospinal fluid (CSF) analysis may serve as a diagnostic test for the screening of epilepsy in sporadic prodromal Alzheimer's disease (AD).Methods: A total of 29 patients with epileptic prodromal sporadic AD patients (epADs) were included and were retrospectively compared with 38 non-epileptic prodromal AD patients (nepADs) for demographics, clinical features, Mini-Mental Status Examination (MMSE) results, CSF biomarkers, and electro-radiological features.Results: Our study did not show any significant differences in CSF biomarkers regarding neurodegeneration, albumin levels, and inflammation between epADs and nepADs. The epADs were significantly older at diagnosis (p = 0.001), more hypertensive (p = 0.01), and displayed larger white matter hyperintensities on brain magnetic resonance imaging (MRI; p = 0.05). There was a significant correlation between the CSF Aβ-42 and Aβ-40 levels with interictal epileptiform discharges and delta slowing on EEGs recordings, respectively (p = 0.03).Conclusions: Our study suggests that CSF may not serve as a surrogate marker of epilepsy in prodromal AD and cannot circumvent the operator-dependent and time-consuming interpretation of EEG recordings. In humans, AD-related epileptogenesis appears to involve the Aβ peptides but likely also additional non-amyloid factors such as small-vessel disease (i.e., white matter hyperintensities).

scholarly journals White Matter Changes in Patients with Alzheimer’s Disease and Associated Factors

2019 ◽  
Vol 8 (2) ◽  
pp. 167 ◽  
Author(s):  
Yi-Hui Kao ◽  
Mei-Chuan Chou ◽  
Chun-Hung Chen ◽  
Yuan-Han Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Rating Scale ◽  
Beta Amyloid ◽  
Future Research ◽  
White Matter Changes ◽  
Age Related ◽  
And Gender ◽  
Fazekas Scale

Alzheimer’s disease (AD) is traditionally thought of as a neurodegenerative disease. Recent evidence shows that beta amyloid-independent vascular changes and beta amyloid-dependent neuronal dysfunction both equally influence the disease, leading to loss of structural and functional connectivity. White matter changes (WMCs) in the brain are commonly observed in dementia patients. The effect of vascular factors on WMCs and the relationship between WMCs and severity of AD in patients remain to be clarified. We recruited 501 clinically diagnosed probable AD patients with a series of comprehensive neuropsychological tests and brain imaging. The WMCs in cerebral CT or MRI were rated using both the modified Fazekas scale and the combined CT-MRI age related WMC (ARWMC) rating scale. Periventricular WMCs were observed in 79.4% of the patients and deep WMCs were also seen in 48.7% of the patients. WMC scores were significantly higher in the advanced dementia stage in periventricular WMCs (p = 0.001) and total ARWMCs (p < 0.001). Age and disease severity were both independently associated with WMCs score, particularly in the total, frontal and parieto-occipital areas. Vascular factors including hypertension, diabetes mellitus, and gender were not significantly associated with WMCs. In conclusion, both age and severity of dementia were significantly associated with WMCs in AD patients. These associations highlight future research targets.

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 Striatal Hypodensities, Not White Matter Hypodensities on CT, Are Associated with Late-Onset Depression in Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Jessica A. Brommelhoff ◽  
Bryan M. Spann ◽  
John L. Go ◽  
Wendy J. Mack ◽  
Margaret Gatz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Frontal Lobe ◽  
Gray Matter ◽  
Late Onset ◽  
Subcortical White Matter ◽  
Ct Scans ◽  
Deep White Matter ◽  
Depression History

This study examined whether there were neuroanatomical differences evident on CT scans of individuals with dementia who differed on depression history. Neuroanatomical variables consisted of visual ratings of frontal lobe deep white matter, subcortical white matter, and subcortical gray matter hypodensities in the CT scans of 182 individuals from the Study of Dementia in Swedish Twins who were diagnosed with dementia and had information on depression history. Compared to individuals with Alzheimer's disease and no depression, individuals with Alzheimer's disease and late-onset depression (first depressive episode at age 60 or over) had a greater number of striatal hypodensities (gray matter hypodensities in the caudate nucleus and lentiform nucleus). There were no significant differences in frontal lobe deep white matter or subcortical white matter. These findings suggest that late-onset depression may be a process that is distinct from the neurodegenerative changes caused by Alzheimer's disease.

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