Investigation of Lewy pathology in the visual pathway of brains of dementia with Lewy bodies

Yamamoto, Ryo; Iseki, Eizo; Murayama, Norio; Minegishi, Michiko; Marui, Wami; Togo, Takashi; Katsuse, Omi; Kato, Masanori; Iwatsubo, Takeshi; Kosaka, Kenji; Arai, Heii

doi:10.1016/j.jns.2006.02.016

Cited by 47 publications

(52 citation statements)

References 25 publications

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“…In addition, a strong correlation between optic nerve and occipital cortex pathology was observed, which, however, showed only a trend towards significance probably due to the small sample size. A study using ␣-synuclein immunohistochemistry examining the visual pathway of 19 DLB cases described mild cell loss in the LGN; however, in contrast to our study they did not detect Lewy bodies or neurites in the LGN and only single neurites in the primary visual cortex and some more positivity in the secondary visual cortex [42]. Whether, this discrepancy is due to different anti-␣-synuclein antibodies used or to a different patient cohort in our and their study is not clear.…”

Section: Discussioncontrasting

confidence: 99%

“…Furthermore, it must be noted that serial sectioning is recommended in cases where the optic nerve or LGN does not show any immunoreactivity. Thus, our study expands their observations [42] and supports the concept of the involvement of the retino-geniculo-occipital in addition to the retinocolliculo-thalamo-amygdala pathway, which could be one explanation for visual hallucinations and dysfunction in PD patients [42,43].…”

Section: Discussionsupporting

confidence: 88%

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Patterns of Tau and α-Synuclein Pathology in the Visual System

Rahimi

Milenković

Kovács

2015

Journal of Parkinson’s Disease

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Abstract.Background: Spreading of misfolded proteins has been suggested for neurodegenerative diseases. The hierarchical distribution of protein deposits in Alzheimer's (AD) and Parkinson's disease (PD) supports this concept. Objectives: To evaluate ␣-synuclein and tau-deposition in the optic pathway as an excellent anatomical model, which follows a strict trajectory including a cortico-geniculate feedback connection. Methods: We immunostained the optic nerve, lateral geniculate nucleus (LGN), and occipital cortex for AT8 (phosphorylated tau), ␣-synuclein, and disease-associated prion protein (PrP) in 47 cases with tau pathology (AD type, argyrophilic grain disease, or progressive supranuclear palsy), 16 PD, and 5 Creutzfeldt-Jakob disease (CJD) cases, respectively. Results: We detected immunoreactivity for all proteins along the optic pathway. The optic nerve showed immunopositivity only in cases with tau (6/8, 75%) or ␣-synuclein (5/7, 71%) pathology. The LGN was involved also frequently (tau: 22/47, 46.8%; ␣-synuclein: 15/16, 93.7%; PrP 5/5, 100%). The occipital cortex was variably affected by tau or ␣-synuclein pathology, but always showed PrP immunoreactivity in the CJD cases. Tau pathology in the LGN correlated with tau immunoreactivity in the occipital cortex and Braak stages of neurofibrillary degeneration. In tauopathies, which do not involve the occipital cortex, like argyrophilic grain disease or progressive supranuclear palsy, tau pathology was more frequently astrocytic in the LGN. Conclusions: Our results have implications 1) for the understanding of disease spreading along neural pathways and 2) for the diagnostic evaluation of the visual system in neurodegenerative proteinopathies as a potential biomarker to evaluate disease progression or subgrouping of cases.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 88%

Patterns of Tau and α-Synuclein Pathology in the Visual System

Rahimi

Milenković

Kovács

2015

Journal of Parkinson’s Disease

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“…Dysfunction of the visuo-amygdaloid pathway has been implicated in the visual misidentification and visual hallucinations. 35,36 In the current study, diffusivity was significantly higher in the inferior longitudinal fasciculi of patients with DLB who were experiencing visual hallucinations compared to the patients with DLB who did not have this symptom, suggesting that visual hallucinations in DLB may be associated with the disruption of the temporo-occipital projections.…”

Section: Resultsmentioning

confidence: 43%

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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“…Visual hallucinations occurred in 62% of our LBD subjects but only in 9.5% of our PD and AD subjects. Visual hallucinations are thought to be more common in LBD subjects due to alpha-synuclein proteinopathy involving the visual processing posterior cortical regions and the limbic areas [55]. More research is required to fully understand the pathophysiology of the behavioral disturbances.…”

Section: Differentiation Of Pd and Ad From Lbd Subjects Based On Automentioning

confidence: 99%

Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases

Scharre

Chang

Nagaraja

et al. 2016

JAD

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Abstract. Limited data compares clinical profiles of Lewy Body Dementia (LBD) with Alzheimer's disease (AD) andParkinson's disease (PD). Twenty-one mildly demented ambulatory LBD subjects were individually matched by MMSE score with 21 AD subjects and by UPDRS motor score with 21 PD subjects. Matched by age, gender, education, and race, pairs were compared using cognitive, functional, behavioral, and motor measures. LBD group performed worse than PD on axial motor, gait, and balance measures. AD had more amnesia and orientation impairments, but less executive and visuospatial deficits than LBD subjects. LBD group had more sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea than AD or PD. Axial motor, gait, and balance disturbances correlated with executive, visuospatial, and global cognition deficits. LBD is differentiated from AD and PD by retrieval memory, visuospatial, and executive deficits; axial motor, gait and balance impairments; sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea.

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Investigation of Lewy pathology in the visual pathway of brains of dementia with Lewy bodies

Cited by 47 publications

References 25 publications

Patterns of Tau and α-Synuclein Pathology in the Visual System

Patterns of Tau and α-Synuclein Pathology in the Visual System

Dementia with Lewy bodies and Alzheimer disease

Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer’s and Parkinson’s Diseases

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