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

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 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.

Abstract WP262: White Matter Stroke and Alzheimer’s Pathology Synergize to Worsen Outcomes in the First Clinically Relevant Mouse Model of Mixed Vascular and Alzheimer’s Disease Dementia

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Julia Huang ◽  
Stefanie Nunez ◽  
Gregory Cole ◽  
Edmond Teng ◽  
Jason D Hinman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Subcortical White Matter ◽  
Molecular Organization ◽  
Plaque Burden ◽  
Mixed Dementia ◽  
Relevant Model ◽  
Amyloid Pathology ◽  
Co Morbidity

Introduction: Microvascular stroke and Alzheimer’s disease (AD) account for the majority of dementia diagnoses with 50% of patients having mixed dementia with features of both microvascular stroke in white matter and AD pathology. Clinico-pathologic studies indicate that white matter hyperintensities present on magnetic resonance imaging correlate with the degree of AD pathology in patients supporting pathologic overlap. This significant co-morbidity indicates an interactive neurobiologic relationship yet it is unclear if these two pathologies synergize or simply co-exist. Prior studies to model stroke and AD pathology have struggled to identify clinically relevant paradigms and time courses that could reasonably link the two disorders. Hypothesis: Subcortical white matter stroke synergizes with AD to worsen outcomes. Methods: We have established a clinically relevant model of mixed dementia by introducing subcortical white matter stroke into EFAD transgenic mice that harbor 5 common AD-associated mutations and knock-in human ApoE alleles under control of the murine ApoE promoter. Strokes were introduced either before or after significant amyloid plaque accumulation and the additive effect of stroke determined. Results: In E4FAD mice (with ApoE4 allele) that have already developed amyloid pathology (>6 months of age), white matter strokes are 70% larger in size (p=0.06) but not associated with worsening gliosis or impaired survival of oligodendrocytes in the peri-infarct region. The molecular organization of axons adjacent to stroke is markedly worse in mice with AD pathology. In younger E4FAD mice, the introduction of a white matter stroke prior to the significant accumulation of amyloid pathology results in worsening plaque burden both globally and in overlying cortex. Conclusions: These data suggest that AD and white matter stroke synergize to worsen both the outcome of stroke occurring in the setting of AD. Similarly early stroke synergizes with amyloid generation to accelerate plaque deposition. This clinically relevant model of mixed dementia will be useful in both preclinical drug disease for both AD and stroke therapies as well as crucial to the discovery of neurobiologic pathways that combine to promote stroke and AD pathologies.

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