LIVIVO - Search results -

Search results

Result 1 - 10 of total 10

Search options

Article ; Online: Roy O. Weller.

Nicoll, James Ar

2022 Volume 48, Issue 7, Page(s) e12848

Language	English
Publishing date	2022-10-05
Publishing country	England
Document type	Journal Article
ZDB-ID	80371-6
ISSN	1365-2990 ; 0305-1846
ISSN (online)	1365-2990
ISSN	0305-1846
DOI	10.1111/nan.12848
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1241: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: Hypothesis: Entrapment of lipoprotein particles in the brain causes Alzheimer's disease.

Boche, Delphine / Nicoll, James Ar

Free neuropathology

2021 Volume 2

Abstract: We present for consideration a hypothesis that impaired movement of lipoprotein particles in the extracellular space in the brain in ageing is central to and causes all the key pathophysiological features of Alzheimer's disease (AD). The role of ... ...

Abstract	We present for consideration a hypothesis that impaired movement of lipoprotein particles in the extracellular space in the brain in ageing is central to and causes all the key pathophysiological features of Alzheimer's disease (AD). The role of lipoprotein particles is to transport cholesterol from glial cells, where it is synthesised, to neurons, which require cholesterol for synaptic plasticity. The lipoprotein particles have a cholesterol-containing hydrophobic core, in which amyloid-β (Aβ) can be solubilised. The core is surrounded by a hydrophilic surface containing apolipoprotein E (APOE) which, as neurons bear receptors for APOE, determines the destination of the particles. The problem arises because the extracellular space is a narrow cleft, barely wider than the lipoprotein particles themselves, which they have to navigate in order to perform their crucial cholesterol-transporting function. We explain how lipoprotein particles could become trapped in the ageing extracellular matrix and that this primary abnormality results in reduced delivery of cholesterol to neurons leading to impaired synaptic plasticity, crucial for learning and memory. It can also explain extracellular Aβ accumulation, to which a microglial response generates a neurotoxic reaction, and intraneuronal tau aggregation, each of which exacerbate the problem. All these players have been known for many years to be important in Alzheimer's pathogenesis but a single unifying mechanism to explain how they are linked has been lacking. This proposed mechanism, with entrapment of lipoproteins particles as key to the development of AD, can explain the failure of so many clinical trials and points out new directions to be taken.
Language	English
Publishing date	2021-11-02
Publishing country	Germany
Document type	Journal Article
ISSN	2699-4445
ISSN (online)	2699-4445
DOI	10.17879/freeneuropathology-2021-3459
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Corticosteroid-responsive focal granulomatous herpes simplex type-1 encephalitis in adults

Varatharaj, Aravinthan / Nicoll, James Ar / Pelosi, Emanuela / Pinto, Ashwin A

Practical neurology

2017 Volume 17, Issue 2, Page(s) 140–144

Abstract: We describe corticosteroid-responsive focal granulomatous encephalitis as a manifestation of herpes simplex virus (HSV) type 1 disease in the brain: something easily missed and easily treated. Two adult cases presented with cognitive symptoms progressing ...

Abstract	We describe corticosteroid-responsive focal granulomatous encephalitis as a manifestation of herpes simplex virus (HSV) type 1 disease in the brain: something easily missed and easily treated. Two adult cases presented with cognitive symptoms progressing over weeks, despite aciclovir treatment. Brain imaging showed temporal lobe abnormalities, with gadolinium enhancement but no abnormal diffusion restriction. HSV-1 PCR analysis was negative in cerebrospinal fluid (CSF) but positive in brain biopsies, which showed vasocentric granulomatous inflammation. Paired blood and CSF samples showed intrathecal synthesis of HSV-1 type-specific IgG. The patients improved clinically only after immunosuppression. Despite profound cognitive impairment at their clinical nadir, both patients recovered fully. We suggest that, at least in a subset of patients with HSV-1 encephalitis, adjunctive corticosteroid treatment is critical to improve the outcome of the disease.
MeSH term(s)	Acyclovir/therapeutic use ; Adrenal Cortex Hormones/therapeutic use ; Antiviral Agents/therapeutic use ; Encephalitis, Herpes Simplex/diagnostic imaging ; Encephalitis, Herpes Simplex/drug therapy ; Female ; Herpesvirus 1, Human/pathogenicity ; Humans ; Magnetic Resonance Imaging ; Middle Aged
Chemical Substances	Adrenal Cortex Hormones ; Antiviral Agents ; Acyclovir (X4HES1O11F)
Language	English
Publishing date	2017-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2170881-2
ISSN	1474-7766 ; 1474-7758
ISSN (online)	1474-7766
ISSN	1474-7758
DOI	10.1136/practneurol-2016-001474
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6001: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Prenatal high-fat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring.

Hawkes, Cheryl A / Gentleman, Steve M / Nicoll, James Ar / Carare, Roxana O

The Journal of pathology

2015 Volume 235, Issue 4, Page(s) 619–631

Abstract: Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) peptides in the extracellular spaces of the brain as plaques and in the walls of blood vessels as cerebral amyloid angiopathy (CAA). Failure of perivascular drainage of Aβ ... ...

Abstract	Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) peptides in the extracellular spaces of the brain as plaques and in the walls of blood vessels as cerebral amyloid angiopathy (CAA). Failure of perivascular drainage of Aβ along cerebrovascular basement membranes contributes to the development of CAA. Mid-life hypercholesterolaemia is a risk factor for the development of AD. Maternal obesity is associated with the development of obesity, hypertension and hypercholesterolaemia in adulthood, suggesting that the risk for AD and CAA may also be influenced by the early-life environment. In the present study, we tested the hypothesis that early-life exposure to a high-fat diet results in changes to the cerebrovasculature and failure of Aβ clearance from the brain. We also assessed whether vascular Aβ deposition is greater in the brains of aged humans with a history of hyperlipidaemia, compared to age-matched controls with normal lipidaemia. Using a mouse model of maternal obesity, we found that exposure to a high-fat diet during gestation and lactation induced changes in multiple components of the neurovascular unit, including a down-regulation in collagen IV, fibronectin and apolipoprotein E, an up-regulation in markers of astrocytes and perivascular macrophages and altered blood vessel morphology in the brains of adult mice. Sustained high-fat diet over the entire lifespan resulted in additional decreases in levels of pericytes and impaired perivascular clearance of Aβ from the brain. In humans, vascular Aβ load was significantly increased in the brains of aged individuals with a history of hypercholesterolaemia. These results support a critical role for early dietary influence on the brain vasculature across the lifespan, with consequences for the development of age-related cerebrovascular and neurodegenerative diseases.
MeSH term(s)	Age Factors ; Alzheimer Disease/etiology ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Animal Nutritional Physiological Phenomena ; Animals ; Basement Membrane/metabolism ; Brain/metabolism ; Brain/pathology ; Case-Control Studies ; Cerebral Amyloid Angiopathy/etiology ; Cerebral Amyloid Angiopathy/metabolism ; Cerebral Amyloid Angiopathy/pathology ; Cerebral Arteries/metabolism ; Cerebral Arteries/pathology ; Cholesterol/metabolism ; Diet, High-Fat/adverse effects ; Extracellular Matrix Proteins/metabolism ; Female ; Gestational Age ; Humans ; Hypercholesterolemia/complications ; Hypercholesterolemia/metabolism ; Maternal Nutritional Physiological Phenomena ; Mice, Inbred C57BL ; Nutritional Status ; Obesity/complications ; Obesity/metabolism ; Obesity/physiopathology ; Plaque, Amyloid ; Pregnancy ; Prenatal Exposure Delayed Effects ; Risk Factors ; Time Factors
Chemical Substances	Amyloid beta-Peptides ; Extracellular Matrix Proteins ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2015-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.4468
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Ud II Zs.12: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Downregulated apoptosis and autophagy after anti-Aβ immunotherapy in Alzheimer's disease.

Paquet, Claire / Nicoll, James Ar / Love, Seth / Mouton-Liger, François / Holmes, Clive / Hugon, Jacques / Boche, Delphine

Brain pathology (Zurich, Switzerland)

2018 Volume 28, Issue 5, Page(s) 603–610

Abstract: Aβ immunization of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ ... ...

Abstract	Aβ immunization of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ immunization, we have assessed the impact of previous Aβ immunization on the expression of a range of apoptotic proteins in post-mortem human brain tissue. Cortex from 13 AD patients immunized with AN1792 (iAD) and from 27 nonimmunized AD (cAD) cases was immunolabeled for proapoptotic proteins implicated in AD pathophysiology: phosphorylated c-Jun N-terminal kinase (pJNK), activated caspase3 (a-casp3), phosphorylated GSK3β on tyrosine 216 (GSK3β
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Alzheimer Disease/therapy ; Alzheimer Vaccines/administration & dosage ; Amyloid beta-Peptides/administration & dosage ; Amyloid beta-Peptides/antagonists & inhibitors ; Amyloid beta-Peptides/immunology ; Apoptosis/immunology ; Autophagy/immunology ; Cerebral Cortex/metabolism ; Cerebral Cortex/pathology ; Down-Regulation/immunology ; Female ; Humans ; Immunization ; Male ; Middle Aged ; Peptide Fragments/antagonists & inhibitors ; Peptide Fragments/immunology ; Retrospective Studies
Chemical Substances	AN-1792 ; Alzheimer Vaccines ; Amyloid beta-Peptides ; Peptide Fragments ; amyloid beta-protein (1-42)
Language	English
Publishing date	2018-02-06
Publishing country	Switzerland
Document type	Clinical Trial ; Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.12567
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 3585: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Metaflammasome components in the human brain: a role in dementia with Alzheimer's pathology?

Taga, Mariko / Minett, Thais / Classey, John / Matthews, Fiona E / Brayne, Carol / Ince, Paul G / Nicoll, James Ar / Hugon, Jacques / Boche, Delphine

Brain pathology (Zurich, Switzerland)

2016 Volume 27, Issue 3, Page(s) 266–275

Abstract: Epidemiological and genetic studies have identified metabolic disorders and inflammation as risk factors for Alzheimer's disease (AD). Evidence in obesity and type-2 diabetes suggests a role for a metabolic inflammasome ("metaflammasome") in mediating ... ...

Abstract	Epidemiological and genetic studies have identified metabolic disorders and inflammation as risk factors for Alzheimer's disease (AD). Evidence in obesity and type-2 diabetes suggests a role for a metabolic inflammasome ("metaflammasome") in mediating chronic inflammation in peripheral organs implicating IKKβ (inhibitor of nuclear factor kappa-B kinase subunit beta), IRS1 (insulin receptor substrate 1), JNK (c-jun N-terminal kinase), and PKR (double-stranded RNA protein kinase). We hypothesized that these proteins are expressed in the brain in response to metabolic risk factors in AD. Neocortex from 299 participants from the MRC Cognitive Function and Ageing Studies was analysed by immunohistochemistry for the expression of the phosphorylated (active) form of IKKβ [pSer
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Apolipoproteins E/genetics ; Cohort Studies ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Female ; Humans ; I-kappa B Kinase/metabolism ; Immunohistochemistry ; Insulin Receptor Substrate Proteins/metabolism ; MAP Kinase Kinase 4/metabolism ; Male ; Mental Status Schedule ; Neocortex/metabolism ; Neocortex/pathology ; Phosphorylation ; Polymorphism, Genetic ; Risk Factors ; eIF-2 Kinase/metabolism
Chemical Substances	Apolipoproteins E ; IRS1 protein, human ; Insulin Receptor Substrate Proteins ; EIF2AK2 protein, human (EC 2.7.11.1) ; eIF-2 Kinase (EC 2.7.11.1) ; I-kappa B Kinase (EC 2.7.11.10) ; IKBKB protein, human (EC 2.7.11.10) ; MAP Kinase Kinase 4 (EC 2.7.12.2)
Language	English
Publishing date	2016-06-08
Publishing country	Switzerland
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.12388
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 3585: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Inflammation in Alzheimer's disease: relevance to pathogenesis and therapy.

Zotova, Elina / Nicoll, James Ar / Kalaria, Raj / Holmes, Clive / Boche, Delphine

Alzheimer's research & therapy

2010 Volume 2, Issue 1, Page(s) 1

Abstract: Evidence for the involvement of inflammatory processes in the pathogenesis of Alzheimer's disease (AD) has been documented for a long time. However, the inflammation hypothesis in relation to AD pathology has emerged relatively recently. Even in this ... ...

Abstract	Evidence for the involvement of inflammatory processes in the pathogenesis of Alzheimer's disease (AD) has been documented for a long time. However, the inflammation hypothesis in relation to AD pathology has emerged relatively recently. Even in this hypothesis, the inflammatory reaction is still considered to be a downstream effect of the accumulated proteins (amyloid beta (Abeta) and tau). This review aims to highlight the importance of the immune processes involved in AD pathogenesis based on the outcomes of the two major inflammation-relevant treatment strategies against AD developed and tested to date in animal studies and human clinical trials - the use of anti-inflammatory drugs and immunisation against Abeta.
Language	English
Publishing date	2010-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2506521-X
ISSN	1758-9193 ; 1758-9193
ISSN (online)	1758-9193
ISSN	1758-9193
DOI	10.1186/alzrt24
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Novel association between microglia and stem cells in human gliomas: A contributor to tumour proliferation?

Noorani, Imran / Petty, Gareth / Grundy, Paul L / Sharpe, Geoff / Willaime-Morawek, Sandrine / Harris, Scott / Thomas, Gareth J / Nicoll, James Ar / Boche, Delphine

The journal of pathology. Clinical research

2015 Volume 1, Issue 2, Page(s) 67–75

Abstract: Brain tumour stem cells and microglia both promote the growth of astrocytomas, the commonest form of primary brain tumour, with recent emerging evidence that these cell types may interact in glioma models. It is unclear whether microglia and stem cells ... ...

Abstract	Brain tumour stem cells and microglia both promote the growth of astrocytomas, the commonest form of primary brain tumour, with recent emerging evidence that these cell types may interact in glioma models. It is unclear whether microglia and stem cells are associated in human gliomas. To investigate this question, we used the technique of tissue microarrays to perform a correlative study of a large number of tumour samples. We quantified immunostaining of human astrocytic tumour tissue microarrays (86 patients; World Health Organisation grade II-IV) for microglia Ionized calcium binding adaptor molecule 1 (Iba1) and CD68, and stem cell nestin, SOX2 and CD133. Ki67 was used to assess proliferation and GFAP for astrocytic differentiation. Immunoreactivity for both microglial markers and stem cell markers nestin and SOX2 significantly increased with increasing tumour grade. GFAP was higher in low grade astrocytomas. There was a positive correlation between: (i) both microglial markers and nestin and CD133, (ii) nestin and tumour cell proliferation Ki67 and (iii) both microglial markers and Ki67. SOX2 was not associated with microglia or tumour proliferation. To test the clinical relevance, we investigated the putative association of these markers with clinical outcomes. High expression for nestin and Iba1 correlated with significantly shorter survival times, and high expression for nestin, Iba1, CD68 and Ki67 was associated with faster tumour progression on univariate analysis. On multivariate analysis, nestin, CD133 and Ki67 remained significant predictors of poorer survival, after adjustment for other markers. These results confirm previous in vitro findings, demonstrating their functional relevance as a therapeutic target in humans. This is the first report of a novel correlation between microglia and stem cells that may drive human astrocytic tumour development.
Language	English
Publishing date	2015-01-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2814357-7
ISSN	2056-4538
ISSN	2056-4538
DOI	10.1002/cjp2.7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The biochemical aftermath of anti-amyloid immunotherapy

Nicoll James AR / Masliah Eliezer / Luehrs Dean C / Patton R Lyle / Kalback Walter M / Kokjohn Tyler A / Daugs Ian D / Maarouf Chera L / Sabbagh Marwan N / Beach Thomas G / Castaño Eduardo M / Roher Alex E

Molecular Neurodegeneration, Vol 5, Iss 1, p

2010 Volume 39

Abstract: Abstract Background Active and passive immunotherapy in both amyloid-beta precursor protein (APP) transgenic mice and Alzheimer's Disease (AD) patients have resulted in remarkable reductions in amyloid plaque accumulation, although the degree of amyloid ... ...

Abstract	Abstract Background Active and passive immunotherapy in both amyloid-beta precursor protein (APP) transgenic mice and Alzheimer's Disease (AD) patients have resulted in remarkable reductions in amyloid plaque accumulation, although the degree of amyloid regression has been highly variable. Nine individuals with a clinical diagnosis of AD dementia were actively immunized with the Aβ peptide 1-42 (AN-1792) and subjected to detailed postmortem biochemical analyses. These patients were compared to 6 non-immunized AD cases and 5 non-demented control (NDC) cases. Results All patients were assessed for the presence of AD pathology including amyloid plaques, neurofibrillary tangles and vascular amyloidosis. This effort revealed that two immunotherapy recipients had dementia as a consequence of diseases other than AD. Direct neuropathological examination consistently demonstrated small to extensive areas in which amyloid plaques apparently were disrupted. Characterization of Aβ species remnants by ELISA suggested that total Aβ levels may have been reduced, although because the amounts of Aβ peptides among treated individuals were extremely variable, those data must be regarded as tentative. Chromatographic analysis and Western blots revealed abundant dimeric Aβ peptides. SELDI-TOF mass spectrometry demonstrated a substantive number of Aβ-related peptides, some of them with elongated C-terminal sequences. Pro-inflammatory TNF-α levels were significantly increased in the gray matter of immunized AD cases compared to the NDC and non-immunized AD groups. Conclusions Immunotherapy responses were characterized by extreme variability. Considering the broad range of biological variation that characterizes aging and complicates the recognition of reliable AD biomarkers, such disparities will make the interpretation of outcomes derived from epidemiologic and therapeutic investigations challenging. Although in some cases the apparent removal of amyloid plaques by AN-1792 was impressive, proportionate alterations in the clinical progression of AD were not evident. The fact that plaque elimination did not alter the trajectory of decline into dementia suggests the likelihood that these deposits alone are not the underlying cause of dementia.
Keywords	Neurology. Diseases of the nervous system ; RC346-429 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Neurology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2010-10-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The biochemical aftermath of anti-amyloid immunotherapy.

Maarouf, Chera L / Daugs, Ian D / Kokjohn, Tyler A / Kalback, Walter M / Patton, R Lyle / Luehrs, Dean C / Masliah, Eliezer / Nicoll, James Ar / Sabbagh, Marwan N / Beach, Thomas G / Castaño, Eduardo M / Roher, Alex E

Molecular neurodegeneration

2010 Volume 5, Page(s) 39

Abstract: Background: Active and passive immunotherapy in both amyloid-beta precursor protein (APP) transgenic mice and Alzheimer's Disease (AD) patients have resulted in remarkable reductions in amyloid plaque accumulation, although the degree of amyloid ... ...

Abstract	Background: Active and passive immunotherapy in both amyloid-beta precursor protein (APP) transgenic mice and Alzheimer's Disease (AD) patients have resulted in remarkable reductions in amyloid plaque accumulation, although the degree of amyloid regression has been highly variable. Nine individuals with a clinical diagnosis of AD dementia were actively immunized with the Aβ peptide 1-42 (AN-1792) and subjected to detailed postmortem biochemical analyses. These patients were compared to 6 non-immunized AD cases and 5 non-demented control (NDC) cases. Results: All patients were assessed for the presence of AD pathology including amyloid plaques, neurofibrillary tangles and vascular amyloidosis. This effort revealed that two immunotherapy recipients had dementia as a consequence of diseases other than AD. Direct neuropathological examination consistently demonstrated small to extensive areas in which amyloid plaques apparently were disrupted. Characterization of Aβ species remnants by ELISA suggested that total Aβ levels may have been reduced, although because the amounts of Aβ peptides among treated individuals were extremely variable, those data must be regarded as tentative. Chromatographic analysis and Western blots revealed abundant dimeric Aβ peptides. SELDI-TOF mass spectrometry demonstrated a substantive number of Aβ-related peptides, some of them with elongated C-terminal sequences. Pro-inflammatory TNF-α levels were significantly increased in the gray matter of immunized AD cases compared to the NDC and non-immunized AD groups. Conclusions: Immunotherapy responses were characterized by extreme variability. Considering the broad range of biological variation that characterizes aging and complicates the recognition of reliable AD biomarkers, such disparities will make the interpretation of outcomes derived from epidemiologic and therapeutic investigations challenging. Although in some cases the apparent removal of amyloid plaques by AN-1792 was impressive, proportionate alterations in the clinical progression of AD were not evident. The fact that plaque elimination did not alter the trajectory of decline into dementia suggests the likelihood that these deposits alone are not the underlying cause of dementia.
Language	English
Publishing date	2010-10-07
Publishing country	England
Document type	Journal Article
ISSN	1750-1326
ISSN (online)	1750-1326
DOI	10.1186/1750-1326-5-39
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED