Progression and staging of Lewy pathology in brains from patients with dementia with Lewy bodies

Marui, Wami; Iseki, Eizo; Nakai, Toshiki; Miura, Satoshi; Kato, Masanori; Uéda, Kenji; Kosaka, Kenji

doi:10.1016/s0022-510x(02)00006-0

Cited by 128 publications

(87 citation statements)

References 24 publications

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“…26,27 A common pathologic feature of this involvement is spongiosis or microvacuolation. 28,29 Increased intravoxel incoherent motion of water molecules in the microvacuoles may be the underlying pathologic mechanism for the increased diffusivity in the amygdala.…”

Section: Resultsmentioning

confidence: 99%

Dementia with Lewy bodies and Alzheimer disease

et al. 2010

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Objective: To identify the patterns of diffusivity changes in patients with dementia with Lewy bodies (DLB) and Alzheimer disease (AD) and to determine whether diffusion tensor MRI (DTI) is complementary to structural MRI in depicting the tissue abnormalities characteristic of DLB and AD. Methods:We studied clinically diagnosed age-, gender-, and education-matched subjects with DLB (n ϭ 30), subjects with AD (n ϭ 30), and cognitively normal (CN) subjects (n ϭ 60) in a case-control study. DTI was performed at 3T with a fluid-attenuated inversion recovery-based DTI sequence that enabled cortical diffusion measurements. Mean diffusivity (MD) and gray matter (GM) density were measured from segmented cortical regions. Tract-based diffusivity was measured using color-coded fractional anisotropy (FA) maps. Results:Patients with DLB were characterized by elevated MD in the amygdala and decreased FA in the inferior longitudinal fasciculus (ILF). ILF diffusivity was associated with the presence of visual hallucinations (p ϭ 0.007), and amygdala diffusivity was associated with Unified Parkinson's Disease Rating Scale (r ϭ 0.50; p ϭ 0.005) in DLB. In contrast, patients with AD were characterized by elevated MD in the medial temporal, temporal, and parietal lobe association cortices and decreased FA in the fornix, cingulum, and ILF. Amygdala diffusivity was complementary to GM density in discriminating DLB from CN; hippocampal and parahippocampal diffusivity was complementary to GM density in discriminating AD from CN. Conclusion:Increased amygdalar diffusivity in the absence of tissue loss in dementia with Lewy bodies (DLB) may be related to microvacuolation, a common pathology associated with Lewy body disease in the amygdala. Diffusivity measurements were complementary to structural MRI, demonstrating that measures of diffusivity on diffusion tensor MRI are valuable tools for characterizing the tissue abnormalities characteristic of Alzheimer disease and DLB. Neurology ® 2010;74:1814 -1821 GLOSSARY AD ϭ Alzheimer disease; CN ϭ cognitively normal; DLB ϭ dementia with Lewy bodies; DTI ϭ diffusion tensor MRI; FA ϭ fractional anisotropy; FDR ϭ false discovery rate; FLAIR ϭ fluid-attenuated inversion recovery; GM ϭ gray matter; ILF ϭ inferior longitudinal fasciculus; LB ϭ Lewy body; MD ϭ mean diffusivity; RBD ϭ REM sleep behavior disorder; ROI ϭ region of interest; SLF ϭ superior longitudinal fasciculus; TE ϭ echo time; TI ϭ inversion time; TR ϭ repetition time; UPDRS ϭ Unified Parkinson's Disease Rating Scale; WM ϭ white matter.Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer disease (AD).1 Although patients with Lewy body (LB) pathology typically have some AD pathology, 2 noninvasive imaging markers that can distinguish the contribution of these different pathologies to the dementia syndrome may be useful for the differential diagnosis and may provide insight into the pathologic mechanisms underlying these disorders.Diffusion tensor MRI (DTI) provides infor...

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Section: Resultsmentioning

confidence: 99%

Dementia with Lewy bodies and Alzheimer disease

et al. 2010

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“…13 Both the nigral neurons of the nigrosomes and the limbic cortical neurons of layers V and VI (which develop strong, earlier lewy bodies) project exclusively to striosomes. 14,15 The BBB of the striatum is especially fragile, whether to ischemic, osmotic, or other stressors. After unilateral ischemic stress, increased BBB permeability appears in the striatum before any other brain region, both ipsi-and contralaterally.…”

Section: Discussionmentioning

confidence: 99%

Striatal Blood–Brain Barrier Permeability in Parkinson'S Disease

Gray

Woulfe

2015

J Cereb Blood Flow Metab

286

202

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In vivo studies have shown that blood-brain barrier (BBB) dysfunction is involved in the course of Parkinson's disease (PD). However, these have lacked either anatomic definition or the ability to recognize minute changes in BBB integrity. Here, using histologic markers of serum protein, iron, and erythrocyte extravasation, we have shown significantly increased permeability of the BBB in the postcommissural putamen of PD patients. The dense innervation of the striatum by PD-affected regions allows for exploitation of this permeability for therapeutic goals. These results are also discussed in the context of the retrograde transsynaptic hypothesis of PD spread. Keywords: α-synuclein; blood-brain barrier; Parkinson's disease; striatum INTRODUCTION Parkinson's disease (PD) is characterized by aggregation of filamentous or oligomerized α-synuclein and degeneration of specific neuronal regions. According to the dual-hit hypothesis of PD pathogenesis, a microbial or toxic pathogen within the gut lumen and the olfactory mucosa represents the pathogenic agent, with subsequent prion-like spread of pathology, first to the dorsal motor nucleus of the vagus and central olfactory areas, respectively, then to higher centers. The connectional anatomy linking the dorsal motor nucleus and olfactory bulb with higher centers such as the substantia nigra is unproven.We have previously proposed that disease could be spread hematogenously. 1 This is conceivable within the paradigm of retrograde (axon terminal to soma) Lewy pathology spread. 2,3 Almost all regions affected in Braak stage 1 have axon terminals outside the blood-brain barrier (BBB). That same BBB, however, protects the higher-order regions, whose axon terminals reside within the central nervous system, from blood-borne substances. Cell-to-cell spread is a potential mechanism to circumvent this protection but the connectional neuroanatomy is not consistent with the temporal order of Lewy pathology development as it is currently understood.Nigrostriatal dopaminergic neuronal cell bodies develop significant Lewy pathology, but recent studies strongly suggest that α-synuclein aggregation in these cells begins at presynaptic axon terminal in the striatum and spreads retrogradely to nigral

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“…·-synuclein is deposited as neurites in dendrites [26]. Their conclusions were based on the pattern of LP formation in the perforant pathway.…”

Section: The Gamut Of Lpmentioning

confidence: 99%

“…There have been two recent attempts to refine this staging system and to characterize the progression of LP through the brain. The first, by Marui et al [26], examined 27 brains from patients clinically diagnosed with DLB and used ·-synuclein immunochemistry to semiquantitatively characterize the density of LB and LN within the amygdala, the CA2/3 region of the hippocampus, the entorhinal cortex and four areas of the neocortex. The neocortical areas included the transentorhinal, insular, middle temporal and superior frontal cortices, which were divided by cortical layers into 3 parts: layers I-II, layer III and layers V-VI.…”

Section: Staging Of Lpmentioning

confidence: 99%

Pathology and Neurotransmitter Abnormalities of Dementia with Lewy Bodies

Duda¹

2003

Dement Geriatr Cogn Disord

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The neuropathology of dementia with Lewy bodies (DLB) is characterized by the presence of Lewy bodies (LBs) and Lewy neurites (LNs) in specific systems throughout the brainstem, diencephalon, basal ganglia and neocortex. DLB shares many features with Parkinson’s disease (PD) with respect to LB distribution in the brainstem, and there is recent evidence that Lewy pathology (LP), which consists of LBs and LNs, may progress in a systematic fashion through the brain regardless of clinical phenotype. Increasing evidence supports a central role for LNs in Lewy neurodegeneration and engenders a ‘neuritic dystrophy hypothesis’ described herein. LP formation also occurs in Alzheimer’s disease (AD) and other dementias, and it is unclear whether there is a common underlying pathophysiology in these diseases or if the LP merely represents a common final pathway. Cholinergic deficits are evident in both DLB and AD, with reductions in acetylcholine and abnormalities in nicotinic and muscarinic receptor expression in both diseases. Cholinergic deficits are greater in DLB than in AD, although generally there is less brain atrophy in DLB. The lower neurodegeneration and preservation of cholinergic receptors in DLB has important therapeutic implications because patients with DLB (vs. AD) may receive greater benefits from cholinergic pharmacologic therapy. Patients with DLB who display parkinsonian signs have severe dopamine neurotransmitter deficiencies similar to those in patients with PD, although the manifestation of these deficiencies is different. Both groups have striatal dopamine transporter deficiencies, but the striatal dopamine D2 receptors are reduced in DLB patients compared with PD and control subjects. D2 receptor deficiencies in DLB may be the cause of the relative lack of response to levodopa treatment and the severe adverse reaction to neuroleptics in these patients.

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Progression and staging of Lewy pathology in brains from patients with dementia with Lewy bodies

Cited by 128 publications

References 24 publications

Dementia with Lewy bodies and Alzheimer disease

Dementia with Lewy bodies and Alzheimer disease

Striatal Blood–Brain Barrier Permeability in Parkinson'S Disease

Pathology and Neurotransmitter Abnormalities of Dementia with Lewy Bodies

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