Correlation of Microglial Activation with White Matter Changes in Dementia with Lewy Bodies

ABSTRACTDementia with Lewy bodies (DLB) is the second-leading degenerative dementia after Alzheimer’s disase. Neuropathologically, it is characterized by alpha-synuclein protein deposition with variable degree of concurrent Alzheimer pathology. Neuroinflammation is increasingly recognized as a significant contributor of degeneration.Objectiveto examine the relationship between microglial activation as measured with [11C]-PK11195 brain PET and MR diffusion tensor imaging (DTI) in DLB.Methodsnineteen clinically probable DLB and 20 similarly aged controls underwent structural MRI with T1-weighted and 3T DTI sequences. Eighteen DLB subjects also underwent [11C]-PK11195 PET imaging. Tract-Based Spatial Statistics (TBSS) were performed to compare DTI parameters in DLB relative to controls and identify associations of [11C]-PK11195 binding with white matter integrity.ResultsTBSS showed widespread changes in all DTI parameters in the DLB group compared to controls (Threshold Free Cluster Enhancement (TFCE) p < 0.05). [11C]-PK11195 binding in parietal cortices also correlated with widespread lower mean and radial diffusivity (TFCE p < 0.05).ConclusionOur study demonstrates that higher PK11195 binding is associated with a relative preservation of white matter, positioning neuroinflammation as a potential early marker in the DLB pathogenic cascade.

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Attention processing speed impairment in early dementia with Lewy bodies correlates with white matter damage on volumetric and diffusion tensor imaging

Alzheimer s & Dementia ◽

10.1002/alz.042729 ◽

2020 ◽

Vol 16 (S4) ◽

Author(s):

Anne Botzung ◽

Mary Mondino ◽

Vincent Noblet ◽

Nathalie Philippi ◽

Frédéric Blanc

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Processing Speed ◽

Dementia With Lewy Bodies ◽

Diffusion Tensor ◽

Lewy Bodies ◽

White Matter Damage ◽

Early Dementia ◽

And Diffusion

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A comparative analysis of cognitive profiles and white-matter alterations using voxel-based diffusion tensor imaging between patients with Parkinson's disease dementia and dementia with Lewy bodies

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.2009.184747 ◽

2009 ◽

Vol 81 (3) ◽

pp. 320-326 ◽

Cited By ~ 65

Author(s):

J. E Lee ◽

H.-J. Park ◽

B. Park ◽

S. K Song ◽

Y. H Sohn ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Diffusion Tensor Imaging ◽

Comparative Analysis ◽

White Matter ◽

Dementia With Lewy Bodies ◽

Diffusion Tensor ◽

Lewy Bodies ◽

Cognitive Profiles ◽

Parkinson’S Disease Dementia

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Slow Progressive Accumulation of Oligodendroglial Alpha-Synuclein (α-Syn) Pathology in Synthetic α-Syn Fibril-Induced Mouse Models of Synucleinopathy

Journal of Neuropathology & Experimental Neurology ◽

10.1093/jnen/nlz070 ◽

2019 ◽

Vol 78 (10) ◽

pp. 877-890 ◽

Cited By ~ 10

Author(s):

Norihito Uemura ◽

Maiko T Uemura ◽

Angela Lo ◽

Fares Bassil ◽

Bin Zhang ◽

...

Keyword(s):

White Matter ◽

Multiple System Atrophy ◽

Parkinson Disease ◽

Mouse Models ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Alpha Synuclein ◽

Wild Type ◽

Time Points ◽

Progressive Accumulation

Abstract Synucleinopathies are composed of Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Alpha-synuclein (α-Syn) forms aggregates mainly in neurons in PD and DLB, while oligodendroglial α-Syn aggregates are characteristic of MSA. Recent studies have demonstrated that injections of synthetic α-Syn preformed fibrils (PFFs) into the brains of wild-type (WT) animals induce intraneuronal α-Syn aggregates and the subsequent interneuronal transmission of α-Syn aggregates. However, injections of α-Syn PFFs or even brain lysates of patients with MSA have not been reported to induce oligodendroglial α-Syn aggregates, raising questions about the pathogenesis of oligodendroglial α-Syn aggregates in MSA. Here, we report that WT mice injected with mouse α-Syn (m-α-Syn) PFFs develop neuronal α-Syn pathology after short postinjection (PI) intervals on the scale of weeks, while oligodendroglial α-Syn pathology emerges after longer PI intervals of several months. Abundant oligodendroglial α-Syn pathology in white matter at later time points is reminiscent of MSA. Furthermore, comparison between young and aged mice injected with m-α-Syn PFFs revealed that PI intervals rather than aging correlate with oligodendroglial α-Syn aggregation. These results provide novel insights into the pathological mechanisms of oligodendroglial α-Syn aggregation in MSA.

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Correlation of microglial activation with white matter changes in dementia with Lewy bodies

NeuroImage Clinical ◽

10.1016/j.nicl.2020.102200 ◽

2020 ◽

Vol 25 ◽

pp. 102200 ◽

Cited By ~ 3

Author(s):

Nicolas Nicastro ◽

Elijah Mak ◽

Guy B. Williams ◽

Ajenthan Surendranathan ◽

W Richard Bevan-Jones ◽

...

Keyword(s):

White Matter ◽

Dementia With Lewy Bodies ◽

Microglial Activation ◽

Lewy Bodies ◽

White Matter Changes

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White matter integrity in dementia with Lewy bodies: a voxel-based analysis of diffusion tensor imaging

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2015.03.007 ◽

2015 ◽

Vol 36 (6) ◽

pp. 2010-2017 ◽

Cited By ~ 19

Author(s):

Zuzana Nedelska ◽

Christopher G. Schwarz ◽

Bradley F. Boeve ◽

Val J. Lowe ◽

Robert I. Reid ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Dementia With Lewy Bodies ◽

Diffusion Tensor ◽

Lewy Bodies ◽

White Matter Integrity

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Dementia with Lewy bodies

New Oxford Textbook of Psychiatry ◽

10.1093/med/9780199696758.003.0045 ◽

2012 ◽

pp. 361-368

Author(s):

I. G. McKeith

Keyword(s):

Dementia With Lewy Bodies ◽

Case Reports ◽

Lewy Bodies ◽

Lewy Body Disease ◽

Alpha Synuclein ◽

Specific Staining ◽

Japanese Workers ◽

Degenerative Dementia ◽

The 1960S ◽

Cortical Lewy Bodies

Lewy bodies are spherical neuronal inclusions, first described by the German neuropathologist Friederich Lewy while working in Alzheimer's laboratory in Munich in 1912. In 1961, Okazaki published case reports about two elderly men who presented with dementia and died shortly after with severe extrapyramidal rigidity. Autopsy showed Lewy bodies in their cerebral cortex. Over the next 20 years, 34 similar cases were reported, all by Japanese workers. Lewy body disease was thus considered to be a rare cause of dementia, until a series of studies in Europe and North America, in the late 1980s, identified Lewy bodies in the brains of between 15 and 20 per cent of elderly demented cases reaching autopsy. Dementia with Lewy bodies (DLB) is unlikely to be a newly occurring disorder, since re-examination of autopsy material collected from elderly demented patients in Newcastle during the 1960s, reveals cortical Lewy bodies in 17 per cent of cases. The recent recognition of DLB as the second most common form of degenerative dementia in old age is largely due to the widespread use of improved neuropathological techniques, initially antiubiquitin immunocytochemistry, and more recently specific staining for alpha-synuclein which is a core constituent of Lewy bodies and related lesions.

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