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Neuropathology and Pathogenesis of Encephalitis following Amyloid β Immunization in Alzheimer's Disease

Published on Jan 1, 2004in Brain Pathology 6.16
· DOI :10.1111/j.1750-3639.2004.tb00493.x
Isidre Ferrer72
Estimated H-index: 72
(University of Barcelona),
Mercé Boada Rovira1
Estimated H-index: 1
+ 2 AuthorsFrederic Costa-Jussá1
Estimated H-index: 1
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Abstract
Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop β-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non treated transgenic animals im-munization with amyloid β peptide has been initiated in a randomised pilot study in AD. Yet a minority of patients developed a neurological complication consistent with meningoencephalitis and one patient died; the trial has been stopped. Neuropathological examination in that patient showed meningoencephalitis and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid nor regression of tau pathology in neurofibrillary tangles and neuropil threads. The present neuropathological study reports the second case of menigoencephalitis following immunization with amyloid-β peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation- with amyliod deposit regression, and possible molecular bases involved in the inflammatory response following immunization. Inflammatory infiltrates were composed of CD8+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. Characteristic neuropathological findings were focal depletion of diffuse and neuritic plaques, but not of amyloid angiopathy, and the presence of small numbers of extremely dense(collapsed) plaques surrounded by active microglia, and multinucleated giant cells filled with dense Aβ42and Aβ40, in addition to severe small cerebral blood Reduced amyloid burden was accompanied by low amyloid-associated oxidative stress responses (reduced superoxide dismutase-1:SOD-1 expression) and by local inhibition of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau in neurofibrillary tangles and β-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. Furthermore, amyloid reduction was accompanied by increased expression of the PA28α/β inductor, and of LMP7, LMP2 and MECL1 subunits of the immunopro-teasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells.Immunoproteasome subunit expression was accompanied by local presentation of MHC class molecules. Release of antigenic peptides derived from β-amyloid processing may enhance T-cell inflammatory responses accounting for the meningoencephalitis following amyloid-β peptide immunization
  • References (47)
  • Citations (499)
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References47
Newest
Published on Apr 5, 2006in Brain Pathology 6.16
William R. Markesbery109
Estimated H-index: 109
(UK: University of Kentucky),
John M. Carney40
Estimated H-index: 40
There is increasing evidence that free radical damage to brain lipids, carbohydrates, proteins, and DNA is involved in neuron death in neurodegenerative disorders. The largest number of studies have been performed in Alzheimer's disease (AD) where there is considerable support for the oxidative stress hypothesis in the pathogenesis of neuron degeneration. In autopsied brain there is an increase in lipid peroxidation, a decline in polyunsaturated fatty acids (PUFA) and an increase in 4-hydroxynon...
648 Citations Source Cite
Published on May 8, 2003in Journal of Neurochemistry 4.87
D. Ziegler1
Estimated H-index: 1
(HHU: University of Düsseldorf)
Increased oxidative stress has been implicated in the pathogenesis of diabetic polyneuropathy (DPN). Antioxidant treatment with alpha-lipoic acid (ALA) has been shown to prevent or ameliorate experimental diabetic neuropathy, providing the rationale for treatment in humans. A recent meta-analysis including four controlled clinical trials provided evidence that treatment with ALA (600 mg/day i.v.) over 3 weeks is safe and significantly improves both neuropathic symptoms and deficits to a clinical...
4 Citations Source Cite
Published on Apr 1, 2003in Nature Medicine 30.64
James A. R. Nicoll57
Estimated H-index: 57
(Southampton General Hospital),
David Wilkinson31
Estimated H-index: 31
(University of Southampton)
+ 3 AuthorsRoy O. Weller52
Estimated H-index: 52
(Southampton General Hospital)
Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report
1,184 Citations Source Cite
Published on Feb 28, 2003in Journal of Neurochemistry 4.87
Susi Keck2
Estimated H-index: 2
,
Robert Nitsch57
Estimated H-index: 57
+ 1 AuthorsOliver Ullrich33
Estimated H-index: 33
Alzheimer's disease (AD) is characterized neuropathologically by intracellular neurofibrillary tangles (NFTs) formed of tau-based paired helical filaments (PHFs) and extracellular β-amyloid plaques. The degree of Alzheimer dementia correlates with the severity of PHFs and NFTs. As an intraneuronal accumulation of oxidatively damaged proteins has been found in the brains of patients with AD, a dysfunction of the proteasomal system, which degrades damaged proteins, has been assumed to cause protei...
312 Citations Source Cite
Published on Jan 1, 2003in Acta Neuropathologica 18.17
K. Jelli60
Estimated H-index: 60
,
Johannes Attems44
Estimated H-index: 44
Recent epidemiological and clinico-pathological data suggest overlaps between Alzheimer's disease (AD) and cerebrovascular lesions (CVL) that may show some synergistic effects, but the results of studies of the relationship between AD and stroke have been controversial. The objective of this study was to compare the frequency of cerebral infarcts, hemorrhages and minor cerebrovascular lesions in autopsy-confirmed AD and age-matched control brains. Using current routine and immunohistochemical me...
83 Citations Source Cite
Published on Dec 1, 2002in Acta Neuropathologica 18.17
Isidre Ferrer72
Estimated H-index: 72
,
Marta Barrachina27
Estimated H-index: 27
(University of Barcelona),
B. Puig26
Estimated H-index: 26
(University of Barcelona)
Tau phosphorylation was examined in Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) using phospho-specific tau antibodies recognizing the phosphorylated form of Ser202, Ser214 and Ser 396, and antibodies to non-phosphorylated glycogen synthase kinase-3α/β (GSK-3α/β), which regulates phosphorylation at these specific sites on tau and phosphorylated GSK-3βSer9 (GSK-3β-P); this antibody is directed to the inactive form of GSK-...
127 Citations Source Cite
Published on Nov 15, 2002in Science 41.04
Michelle Pfeifer3
Estimated H-index: 3
(University of Basel),
Sonia Boncristiano4
Estimated H-index: 4
(University of Basel)
+ 5 AuthorsMathias Jucker67
Estimated H-index: 67
(University of Basel)
Immunotherapy for Alzheimer's disease (AD) has been the subject of intense investigation. Both active and passive immunization against β-amyloid peptide (Aβ) in mouse models reduce levels of Aβ, prevent and clear amyloid plaques, and improve cognitive behavior ([1][1]). We studied passive
441 Citations Source Cite
Published on Nov 13, 2002in Journal of Neurochemistry 4.87
Mark A. Smith119
Estimated H-index: 119
(Case Western Reserve University),
Keisukehirai25
Estimated H-index: 25
(Case Western Reserve University)
+ 5 AuthorsGeorge Perry121
Estimated H-index: 121
(Case Western Reserve University)
Abstract: Increased awareness for a role of oxidative stress in the pathogenesis of Alzheimer's disease has highlighted the issue of whether oxidative damage is a fundamental step in the pathogenesis or instead results from disease-associated pathology. In vitro experiments support both possibilities: Oxidative stress increases amyloid-β production, and, conversely, amyloid-β increases oxidative damage. To address the relationship between amyloid-β and oxidative stress in vivo, we examined, usin...
491 Citations Source Cite
Published on Nov 1, 2002in Journal of Alzheimer's Disease 3.70
Alex E. Roher57
Estimated H-index: 57
,
Tyler A. Kokjohn29
Estimated H-index: 29
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by a time-dependent amyloid fibril deposition in cortical senile plaques and cerebral vascular walls. Several transgenic (Tg) mice have been engineered to overexpress amyloid-beta precursor protein (AβPP) with familial AD mutations. With advancing age, the Tg mice accumulate amyloidbeta (Aβ) peptides, primarily of 40 to 42 amino acids, in plaques and blood vessel wall deposits which resemble morphologically those ...
10 Citations Source Cite
Published on May 1, 2002in The Journal of Neuroscience 6.07
Mary J. Savage26
Estimated H-index: 26
(Cephalon),
Yin-Guo Lin9
Estimated H-index: 9
(Cephalon)
+ 2 AuthorsRichard W. Scott39
Estimated H-index: 39
(Cephalon)
The mechanisms by which neurons and synapses are lost in Alzheimer's disease (AD) are not completely understood. To characterize potential signaling events linked to AD pathogenesis, activation-specific antibodies were used to examine mitogen-activated protein kinase (MAPK) kinase pathways at various ages in mice transgenic for human amyloid precursor protein-695 with the Swedish familial AD mutations (Tg2576) and homozygous for a P264L familial AD mutation introduced by targeting of the preseni...
210 Citations Source Cite
Cited By499
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Published on Apr 4, 2019in Brain 11.81
Seth Love54
Estimated H-index: 54
(UoB: University of Bristol),
James A. R. Nicoll57
Estimated H-index: 57
+ 6 AuthorsClive Holmes55
Estimated H-index: 55
2 Citations Source Cite
Published on Apr 3, 2019in Expert Review of Vaccines 4.53
Thomas Gerlach1
Estimated H-index: 1
,
Husni Elbahesh1
Estimated H-index: 1
+ 1 AuthorsGuus F. Rimmelzwaan76
Estimated H-index: 76
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Published on Apr 1, 2019in Journal of Biotechnology 3.16
Si Li1
Estimated H-index: 1
(ZJU: Zhejiang University),
Yangyang Jin1
Estimated H-index: 1
(ZSTU: Zhejiang Sci-Tech University)
+ 4 AuthorsZhengbing Lv12
Estimated H-index: 12
(ZSTU: Zhejiang Sci-Tech University)
Abstract Silkworms are an economically important insect.Silkworm pupae are also a nutrient-rich food and can be used as a pharmaceutical intermediate.The N-terminus of Aβ includes 1–15 amino acid residues with a B cell surface antigen that is necessary to produce antibody and prevent the adverse reactions observed in response to the full Aβ42 peptide. In this study, we used silkworm pupae to develop a safer vaccine for Alzheimer’s disease (AD) patients. Aβ15 peptide was fused with the cholera to...
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Published on Apr 1, 2019in Atherosclerosis 4.25
Amir Abbas Momtazi-Borojeni9
Estimated H-index: 9
(MUMS: Mashhad University of Medical Sciences),
Mahmoud Reza Jaafari31
Estimated H-index: 31
(MUMS: Mashhad University of Medical Sciences)
+ 1 AuthorsAmirhossein Sahebkar53
Estimated H-index: 53
(MUMS: Mashhad University of Medical Sciences)
Abstract Background and aims Proprotein convertase subtilisin kexin type 9 (PCSK9) is a liver secretory enzyme that controls plasma low-density lipoprotein cholesterol (LDL-C) levels through modulation of LDL receptor (LDLR). Inhibition of PCSK9 using monoclonal antibodies (mAbs) can efficiently lower plasma LDL-C. However, the relatively short half-life of mAbs necessitates frequent passive immunization, which is costly. These limitations can be circumvented by active immunization. Here, we eva...
3 Citations Source Cite
Published on Jan 1, 2019in Journal of the American Society for Mass Spectrometry 3.20
Matthew A. Downey1
Estimated H-index: 1
(UC: University of California),
Maxwell J. Giammona3
Estimated H-index: 3
(UC: University of California)
+ 3 AuthorsMichael T. Bowers71
Estimated H-index: 71
(UC: University of California)
Alzheimer’s disease (AD) is rapidly reaching epidemic status among a burgeoning aging population. Much evidence suggests the toxicity of this amyloid disease is most influenced by the formation of soluble oligomeric forms of amyloid β-protein, particularly the 42-residue alloform (Aβ42). Developing potential therapeutics in a directed, streamlined approach to treating this disease is necessary. Here we utilize the joint pharmacophore space (JPS) model to design a new molecule [AC0107] incorporat...
1 Citations Source Cite
Published on Dec 1, 2018in Glia 5.83
Wolfgang J. Streit57
Estimated H-index: 57
(UF: University of Florida),
Heiko Braak44
Estimated H-index: 44
(University of Ulm)
+ 6 AuthorsIngo Bechmann53
Estimated H-index: 53
(Leipzig University)
1 Citations Source Cite
Published on Nov 1, 2018in Human Pathology: Case Reports
Takahiro Watanabe6
Estimated H-index: 6
(Hyogo College of Medicine),
Shinichiro Ukon (Hyogo College of Medicine)+ 12 AuthorsYuki Okano (Hyogo College of Medicine)
Abstract A 76-year-old female presented with cognitive impairment and multiple brain infarcts and died of massive subcortical cerebral hemorrhage. A premortem clinical diagnosis was not possible. She did not show apparent microbleeds on brain images during her lifetime. An autopsy revealed vasculitis at various stages with amyloid β deposition and granulomatous reaction in cortical and leptomeningeal arteries, although almost vasculitic processes were in the healing stage, suggestive of the inac...
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Published on Oct 22, 2018in Natural Product Research 2.00
Yingying Cao (Guangzhou University of Chinese Medicine), Wenxing Xu (Guangzhou University of Chinese Medicine)+ 1 AuthorsXing Zeng6
Estimated H-index: 6
(Guangzhou University of Chinese Medicine)
AbstractLicochalcone B (LCB), an extract from the root of Glycyrrhiza inflate, has the same caffeic acid scaffold as curcumin (Cur), which is known as an anti-Alzheimer’s disease (AD) agent. However, there is no relevant research about anti-AD activity of LCB. In this study, the anti-AD activity of LCB was investigated. LCB could inhibit amyloid beta (Aβ42) self-aggregation (IC50 = 2.16 ± 0.24 μM) and disaggregate pre-formed Aβ42 fibrils, reduce metal-induced Aβ42 aggregation through chelating m...
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