scholarly journals Closer correlations between florbetapir PET measurements of amyloid plaque burden using a cerebral white matter reference region and Alzheimer’s disease‐related hypometabolism

2021 ◽  
Vol 17 (S1) ◽  
Author(s):  
Michele S Wang ◽  
Tingting B Bi ◽  
Naomi Y Jing ◽  
Jake C Ausdemore ◽  
Harrison L Kramer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Amyloid Plaque ◽  
Plaque Burden ◽  
Cerebral White Matter ◽  
Reference Region

scholarly journals Microglial-associated responses to comorbid amyloid pathology and hyperhomocysteinemia in an aged knock-in mouse model of Alzheimer’s disease

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
David J. Braun ◽  
Edgardo Dimayuga ◽  
Josh M. Morganti ◽  
Linda J. Van Eldik
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Inflammatory Responses ◽  
Specific Effect ◽  
Amyloid Plaque ◽  
Plaque Burden ◽  
Amyloid Pathology ◽  
Model Of Alzheimer’S Disease ◽  
B Vitamin

Abstract Background Elevated blood homocysteine levels, termed hyperhomocysteinemia (HHcy), is a prevalent risk factor for Alzheimer’s disease (AD) in elderly populations. While dietary supplementation of B-vitamins is a generally effective method to lower homocysteine levels, there is little if any benefit to cognition. In the context of amyloid pathology, dietary-induced HHcy is known to enhance amyloid deposition and certain inflammatory responses. Little is known, however, about whether there is a more specific effect on microglia resulting from combined amyloid and HHcy pathologies. Methods The present study used a knock-in mouse model of amyloidosis, aged to 12 months, given 8 weeks of B-vitamin deficiency-induced HHcy to better understand how microglia are affected in this comorbidity context. Results We found that HHcy-inducing diet increased amyloid plaque burden, altered the neuroinflammatory milieu, and upregulated the expression of multiple damage-associated and “homeostatic” microglial genes. Conclusions Taken together, these data indicate complex effects of comorbid pathologies on microglial function that are not driven solely by increased amyloid burden. Given the highly dynamic nature of microglia, their central role in AD pathology, and the frequent occurrence of various comorbidities in AD patients, it is increasingly important to understand how microglia respond to mixed pathological processes.

scholarly journals Diagnostic Utility of Cerebral White Matter Integrity in Early Alzheimer's Disease

2010 ◽  
Vol 120 (8) ◽  
pp. 544-550 ◽  
Author(s):  
David K. Johnson ◽  
Willis Barrow ◽  
RaeAnn Anderson ◽  
Amith Harsha ◽  
Robyn Honea ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
White Matter Integrity ◽  
Cerebral White Matter ◽  
Diagnostic Utility ◽  
Early Alzheimer’S Disease

Loss of GPR3 reduces the amyloid plaque burden and improves memory in Alzheimer’s disease mouse models

2015 ◽  
Vol 7 (309) ◽  
pp. 309ra164-309ra164 ◽  
Author(s):  
Yunhong Huang ◽  
Aneta Skwarek-Maruszewska ◽  
Katrien Horré ◽  
Elke Vandewyer ◽  
Leen Wolfs ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Amyloid Plaque ◽  
Plaque Burden

scholarly journals Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease

2021 ◽  
Author(s):  
Roland Friedel ◽  
Yong Huang ◽  
Minghui Wang ◽  
Shalaka Wahane ◽  
Mitzy Ríos de Anda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Amyloid Plaque ◽  
Reactive Astrocytes ◽  
Glial Activation ◽  
Plaque Burden ◽  
Aβ Amyloid ◽  
Underlying Mechanisms

Abstract Communication between glial cells has a profound effect on the pathophysiology of Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. Here, we reveal a role of reactive astrocytes in enforcing cell distancing in the glial nets surrounding amyloid plaques, which restricts microglial coverage of Aβ, a prerequisite to detect and engulf amyloid deposits. This process is mediated through guidance receptor Plexin-B1, which we identified as a key network regulator of late-onset AD. We show that Plexin-B1 is robustly upregulated in plaque-associated astrocytes in a corona-like pattern, and its expression levels correlate with plaque burden and disease severity in AD patients. In APP/PS1 mice, an amyloidogenic model of AD, removing Plexin-B1 led to smaller peri-plaque glial nets with relaxed cell distancing and enhanced glial coverage of Aβ plaques, as well as transcriptional changes in both reactive astrocytes and disease-associated microglia that are linked to glial activation and amyloid clearance. Furthermore, amyloid plaque burden was lowered, together with a shift towards dense-core plaques and reduced neuritic dystrophy. Our data thus support a role of Plexin-B1 in controlling glial net structure by imposing cell distancing, leading to poor glial coverage of Aβ, reduced amyloid clearance and compaction. Relaxing cell distancing by targeting guidance receptors may present an alternative strategy to alleviate neuroinflammation in AD by improving glial coverage of Aβ amyloid and plaque compaction.

scholarly journals A White Matter Connection of Schizophrenia and Alzheimer’s Disease

2020 ◽  
Author(s):  
Peter Kochunov ◽  
Artemis Zavaliangos-Petropulu ◽  
Neda Jahanshad ◽  
Paul M Thompson ◽  
Meghann C Ryan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Cognitive Deficits ◽  
Vulnerability Index ◽  
Cerebral White Matter ◽  
Cognitive Measures ◽  
Cohen’S D ◽  
Regional Vulnerability ◽  
Cohen's D

Abstract Schizophrenia (SZ) is a severe psychiatric illness associated with an elevated risk for developing Alzheimer’s disease (AD). Both SZ and AD have white matter abnormalities and cognitive deficits as core disease features. We hypothesized that aging in SZ patients may be associated with the development of cerebral white matter deficit patterns similar to those observed in AD. We identified and replicated aging-related increases in the similarity between white matter deficit patterns in patients with SZ and AD. The white matter “regional vulnerability index” (RVI) for AD was significantly higher in SZ patients compared with healthy controls in both the independent discovery (Cohen’s d = 0.44, P = 1·10–5, N = 173 patients/230 control) and replication (Cohen’s d = 0.78, P = 9·10–7, N = 122 patients/64 controls) samples. The degree of overlap with the AD deficit pattern was significantly correlated with age in patients (r = .21 and .29, P < .01 in discovery and replication cohorts, respectively) but not in controls. Elevated RVI-AD was significantly associated with cognitive measures in both SZ and AD. Disease and cognitive specificities were also tested in patients with mild cognitive impairment and showed intermediate overlap. SZ and AD have diverse etiologies and clinical courses; our findings suggest that white matter deficits may represent a key intersecting point for these 2 otherwise distinct diseases. Identifying mechanisms underlying this white matter deficit pattern may yield preventative and treatment targets for cognitive deficits in both SZ and AD patients.

Sign in / Sign up

Export Citation Format

Share Document