Vacuolar Change in Alzheimer's Disease

Smith, Thomas W.; Anwer, Ursula E.; DeGirolami, Umberto; Drachman, David A.

doi:10.1001/archneur.1987.00520240007003

Cited by 47 publications

(19 citation statements)

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“…39 It is possible that an additional pathologic process may be contributing to the elevated diffusivity in the medial temporal lobe regions severely affected with the neurodegenerative pathology of AD such as vacuolization. 28,40 It is not obvious in which direction vacuolization might influence the tissue volume, but vacuolization should increase diffusivity, providing additional information over atrophy.…”

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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“…Dendrite swelling has been described previously in the spinal cord of SOD1(G93A) mice . Furthermore, neuropil vacuolization is also a typical hallmark of prion diseases, such as sporadic Creutzfeldt–Jakob disease (sCJD), but similar spongiform changes have also been described for other neurodegenerative diseases including Alzheimer's disease , dementia with Lewy bodies and FTD . Though, artifacts produced by poor fixation and tissue processing can be ruled out, since no vacuolization was observed in WT mice.…”

Section: Discussionmentioning

confidence: 96%

Neurodegeneration and NLRP3 inflammasome expression in the anterior thalamus of SOD1(G93A) ALS mice

et al. 2017

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Nowadays, amyotrophic lateral sclerosis (ALS) is considered as a multisystem disorder, characterized by a primary degeneration of motor neurons as well as neuropathological changes in non-motor regions. Neurodegeneration in subcortical areas, such as the thalamus, are believed to contribute to cognitive and behavioral abnormalities in ALS patients. In the present study, we investigated neurodegenerative changes including neuronal loss and glia pathology in the anterodorsal thalamic nucleus (AD) of SOD1(G93A) mice, a widely used animal model for ALS. We detected massive dendrite swelling and neuronal loss in SOD1(G93A) animals, which was accompanied by a mild gliosis. Furthermore, misfolded SOD1 protein and autophagy markers were accumulating in the AD. Since innate immunity and activation inflammasomes seem to play a crucial role in ALS, we examined protein expression of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) and the cytokine interleukin 1 beta (IL1β) in AD glial cells and neurons. NLRP3 and ASC were significantly up-regulated in the AD of SOD1(G93A) mice. Finally, co-localization studies revealed expression of NLRP3, ASC and IL1β in neurons. Our study yielded two main findings: (i) neurodegenerative changes already occur at an early symptomatic stage in the AD and (ii) increased inflammasome expression may contribute to neuronal cell death. In conclusion, neurodegeneration in the anterior thalamus may critically account for cognitive changes in ALS pathology.

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“…Many different neuronal systems are compromised in AD (Mann and Yates, 1986; Hauw and Duyckaerts, 2001), some more markedly than others, and synapses are regionally depleted (Terry et al, 1999; Duyckaerts et al, 2009). In some cases of AD, spongiform change is evident that, though generally less severe, can resemble that seen in CJD (Smith et al, 1987; Sherzai et al, 2013) (Figure 2). As noted above, other neurodegenerative conditions might be present in the brain along with the lesions of AD, particularly in older patients.…”

Section: The Neuropathology Of Ad In the Context Of The Prion Paradigmmentioning

confidence: 96%

“…Spongiform change is not unique to prion diseases, but it is less common in AD, and when it occurs it is generally mild (Smith et al, 1987; Sherzai et al, 2013). Hematoxylin and eosin stain.…”

Section: Figurementioning

confidence: 99%

Prion-like mechanisms in Alzheimer disease

Walker

2018

Handbook of Clinical Neurology

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Senile plaques and neurofibrillary tangles are the principal histopathologic hallmarks of Alzheimer disease. The essential constituents of these lesions are structurally abnormal variants of normally generated proteins: Aβ protein in plaques and tau protein in tangles. At the molecular level, both proteins in a pathogenic state share key properties with classic prions, i.e., they consist of alternatively folded, β-sheet-rich forms of the proteins that autopropagate by the seeded corruption and self-assembly of like proteins. Other similarities with prions include the ability to manifest as polymorphic and polyfunctional strains, resistance to chemical and enzymatic destruction, and the ability to spread within the brain and from the periphery to the brain. In Alzheimer disease, current evidence indicates that the pathogenic cascade follows from the endogenous, sequential corruption of Aβ and then tau. Therapeutic options include reducing the production or multimerization of the proteins, uncoupling the Aβ-tauopathy connection, or promoting the inactivation or removal of anomalous assemblies from the brain. Although aberrant Aβ appears to be the prime mover of Alzheimer disease pathogenesis, once set in motion by Aβ, the prion-like propagation of tauopathy may proceed independently of Aβ; if so, Aβ might be solely targeted as an early preventive measure, but optimal treatment of Alzheimer disease at later stages of the cascade could require intervention in both pathways.

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Vacuolar Change in Alzheimer's Disease

Cited by 47 publications

References 9 publications

Dementia with Lewy bodies and Alzheimer disease

Dementia with Lewy bodies and Alzheimer disease

Neurodegeneration and NLRP3 inflammasome expression in the anterior thalamus of SOD1(G93A) ALS mice

Prion-like mechanisms in Alzheimer disease

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