Progression of White Matter Hyperintensities in Alzheimer Disease, Dementia With Lewy Bodies, and Parkinson Disease Dementia: A Comparison With Normal Aging

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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Depression and Synaptic Zinc Regulation in Alzheimer Disease, Dementia with Lewy Bodies, and Parkinson Disease Dementia

American Journal of Geriatric Psychiatry ◽

10.1016/j.jagp.2014.05.001 ◽

2015 ◽

Vol 23 (2) ◽

pp. 141-148 ◽

Cited By ~ 27

Author(s):

David R. Whitfield ◽

Julie Vallortigara ◽

Amani Alghamdi ◽

Tibor Hortobágyi ◽

Clive Ballard ◽

...

Keyword(s):

Alzheimer Disease ◽

Parkinson Disease ◽

Dementia With Lewy Bodies ◽

Lewy Bodies

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Utility of Autonomic Function Tests to Differentiate Dementia with Lewy Bodies and Parkinson Disease with Dementia from Alzheimer Disease

European Neurology ◽

10.1159/000484409 ◽

2017 ◽

Vol 79 (1-2) ◽

pp. 27-32 ◽

Cited By ~ 5

Author(s):

Shuta Toru ◽

Tadashi Kanouchi ◽

Takanori Yokota ◽

Yosuke Yagi ◽

Akira Machida ◽

...

Keyword(s):

Alzheimer Disease ◽

Parkinson Disease ◽

Dementia With Lewy Bodies ◽

Autonomic Function ◽

Lewy Bodies ◽

Sympathetic Skin Response ◽

Tilt Test ◽

Autonomic Function Tests ◽

Function Tests ◽

Skin Response

Objective: We studied autonomic disturbance in patients with dementia with Lewy bodies (DLB), Parkinson disease with dementia (PDD), Alzheimer disease (AD), to determine whether autonomic function tests can be used to distinguish these disorders. Methods: Autonomic function was tested in 56 patients with DLB, 37 patients with PDD, and 59 patients with AD by using the sympathetic skin response, coefficient of variation in R-R interval, the head-up tilt test, serum norepinephrine concentration, and 123I-meta-iodobenzylguanidine cardiac scintigraphy. Symptoms of autonomic dysfunction, such as constipation, urinary symptoms, and orthostatic hypotension, were also noted. Results: The groups did not differ on baseline characteristics other than those associated with Parkinsonism and dementia. All patients with DLB and PDD had some dysautonomia, whereas rates were much lower for patients with AD (19%). Significantly more DLB and PDD patients than AD patients showed abnormalities on autonomic function tests. Conclusions: Autonomic function tests might be quite useful to distinguish DLB and PDD from AD.

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