LIVIVO - Search results -

Search results

Result 1 - 10 of total 35

Search options

Article ; Online: Transgenic mouse models of Alzheimer disease: developing a better model as a tool for therapeutic interventions.

Kitazawa, Masashi / Medeiros, Rodrigo / Laferla, Frank M

2012 Volume 18, Issue 8, Page(s) 1131–1147

Abstract: Alzheimer disease (AD) is the leading cause of dementia among elderly. Currently, no effective treatment is available for AD. Analysis of transgenic mouse models of AD has facilitated our understanding of disease mechanisms and provided valuable tools ... ...

Abstract	Alzheimer disease (AD) is the leading cause of dementia among elderly. Currently, no effective treatment is available for AD. Analysis of transgenic mouse models of AD has facilitated our understanding of disease mechanisms and provided valuable tools for evaluating potential therapeutic strategies. In this review, we will discuss the strengths and weaknesses of current mouse models of AD and the contribution towards understanding the pathological mechanisms and developing effective therapies.
MeSH term(s)	Aged ; Alzheimer Disease/drug therapy ; Alzheimer Disease/physiopathology ; Animals ; Disease Models, Animal ; Drug Design ; Humans ; Mice ; Mice, Transgenic
Language	English
Publishing date	2012-01-30
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/138161212799315786
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4714: 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

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 ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD.

Kitazawa, Masashi / Cheng, David / Laferla, Frank M

Journal of neurochemistry

2009 Volume 108, Issue 6, Page(s) 1550–1560

Abstract: Excess copper exposure is thought to be linked to the development of Alzheimer's disease (AD) neuropathology. However, the mechanism by which copper affects the CNS remains unclear. To investigate the effect of chronic copper exposure on both beta- ... ...

Abstract	Excess copper exposure is thought to be linked to the development of Alzheimer's disease (AD) neuropathology. However, the mechanism by which copper affects the CNS remains unclear. To investigate the effect of chronic copper exposure on both beta-amyloid and tau pathologies, we treated young triple transgenic (3xTg-AD) mice with 250 ppm copper-containing water for a period of 3 or 9 months. Copper exposure resulted in altered amyloid precursor protein processing; increased accumulation of the amyloid precursor protein and its proteolytic product, C99 fragment, along with increased generation of amyloid-beta peptides and oligomers. These changes were found to be mediated via up-regulation of BACE1 as significant increases in BACE1 levels and deposits were detected around plaques in mice following copper exposure. Furthermore, tau pathology within hippocampal neurons was exacerbated in copper-exposed 3xTg-AD group. Increased tau phosphorylation was closely correlated with aberrant cdk5/p25 activation, suggesting a role for this kinase in the development of copper-induced tau pathology. Taken together, our data suggest that chronic copper exposure accelerates not only amyloid pathology but also tau pathology in a mouse model of AD.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Amyloid/metabolism ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/genetics ; Animals ; Brain/metabolism ; Brain/pathology ; Calpain/metabolism ; Cell Line, Tumor ; Copper/administration & dosage ; Cyclin-Dependent Kinase 5/metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoprecipitation ; Mice ; Mice, Transgenic ; Mutation/genetics ; Peptide Fragments/metabolism ; Superoxide Dismutase/metabolism ; Superoxide Dismutase-1 ; Time Factors ; Trace Elements/administration & dosage ; tau Proteins/metabolism
Chemical Substances	Amyloid ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Peptide Fragments ; SOD1 protein, human ; Trace Elements ; amyloid beta-protein (1-40) ; amyloid beta-protein (1-42) ; tau Proteins ; Copper (789U1901C5) ; Sod1 protein, mouse (EC 1.15.1.1) ; Superoxide Dismutase (EC 1.15.1.1) ; Superoxide Dismutase-1 (EC 1.15.1.1) ; Cyclin-Dependent Kinase 5 (EC 2.7.11.1) ; Calpain (EC 3.4.22.-)
Language	English
Publishing date	2009-01-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.1471-4159.2009.05901.x
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.170: 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: ST101 induces a novel 17 kDa APP cleavage that precludes Aβ generation in vivo.

Green, Kim N / Khashwji, Hasan / Estrada, Tatiana / Laferla, Frank M

Annals of neurology

2011 Volume 69, Issue 5, Page(s) 831–844

Abstract: Objective: Inhibiting Aβ generation is a prime therapeutic goal for preventing or treating Alzheimer disease. Here we sought to identify any disease-modifying properties of an azaindolizinone derivative, spiro[imidazo[1,2-a]pyridine-3,2-idan]-2(3H)-one ( ...

Abstract	Objective: Inhibiting Aβ generation is a prime therapeutic goal for preventing or treating Alzheimer disease. Here we sought to identify any disease-modifying properties of an azaindolizinone derivative, spiro[imidazo[1,2-a]pyridine-3,2-idan]-2(3H)-one (ST101 or ZSET1446). Methods: The effects of ST101 were studied in 3xTg-AD mice and young cynomolgus monkeys using a combination of biochemical and histological analyses. Results: Here we describe that ST101 induces cleavage of APP protein at a novel site, generating a 17 kDa C-terminal fragment. This 17 kDa APP cleavage product does not appear to be a substrate for either α- or β-secretase, and thus bypasses generation of Aβ. ST101 is orally active, efficacious at low doses, improves memory function, and robustly reduces brain Aβ in transgenic mice and nonhuman primates. Interpretation: Using rodent and nonhuman primate models, we show that ST101 represents a novel class of small molecules that reduce central nervous system levels of Aβ by inducing an alternate pathway of APP cleavage.
MeSH term(s)	Age Factors ; Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Amyloidogenic Proteins/drug effects ; Amyloidogenic Proteins/genetics ; Amyloidogenic Proteins/metabolism ; Animals ; Brain/drug effects ; Brain/metabolism ; Brain/ultrastructure ; Cathepsin D/metabolism ; Cell Line, Tumor ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay/methods ; Humans ; Indans/pharmacology ; Macaca fascicularis ; Maze Learning/drug effects ; Memory/drug effects ; Mice ; Mice, Transgenic ; Molecular Weight ; Neuroblastoma/pathology ; Peptide Fragments/metabolism ; Proteomics/methods ; Reaction Time/drug effects ; Schizophrenia/drug therapy ; Schizophrenia/metabolism ; Schizophrenia/pathology ; Spiro Compounds/pharmacology ; Subcellular Fractions/drug effects ; Subcellular Fractions/metabolism ; Transfection ; Tubulin/metabolism ; tau Proteins/genetics
Chemical Substances	Amyloid beta-Protein Precursor ; Amyloidogenic Proteins ; Indans ; Peptide Fragments ; Spiro Compounds ; Tubulin ; amyloid beta-protein precursor C-terminal fragment beta, human ; spiro(imidazo-(1,2-a)pyridine-3,2-indan)-2(3H)-one ; tau Proteins ; Cathepsin D (EC 3.4.23.5)
Language	English
Publishing date	2011-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.22325
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1370: 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)
Zs.MO 478: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The bradykinin B1 receptor regulates Aβ deposition and neuroinflammation in Tg-SwDI mice.

Passos, Giselle F / Medeiros, Rodrigo / Cheng, David / Vasilevko, Vitaly / Laferla, Frank M / Cribbs, David H

The American journal of pathology

2013 Volume 182, Issue 5, Page(s) 1740–1749

Abstract: The deposition of amyloid-β peptides (Aβ) in the cerebral vasculature, a condition known as cerebral amyloid angiopathy, is increasingly recognized as an important component leading to intracerebral hemorrhage, neuroinflammation, and cognitive impairment ...

Abstract	The deposition of amyloid-β peptides (Aβ) in the cerebral vasculature, a condition known as cerebral amyloid angiopathy, is increasingly recognized as an important component leading to intracerebral hemorrhage, neuroinflammation, and cognitive impairment in Alzheimer disease (AD) and related disorders. Recent studies demonstrated a role for the bradykinin B1 receptor (B1R) in cognitive deficits induced by Aβ in mice; however, its involvement in AD and cerebral amyloid angiopathy is poorly understood. Herein, we investigated the effect of B1R inhibition on AD-like neuroinflammation and amyloidosis using the transgenic mouse model (Tg-SwDI). B1R expression was found to be up-regulated in brains of Tg-SwDI mice, specifically in the vasculature, neurons, and astrocytes. Notably, administration of the B1R antagonist, R715, to 8-month-old Tg-SwDI mice for 8 weeks resulted in higher Aβ40 levels and increased thioflavin S-positive fibrillar Aβ deposition. Moreover, blockage of B1R inhibited neuroinflammation, as evidenced by the decreased accumulation of activated microglia and reactive astrocytes, diminished NF-κB activation, and reduced cytokine and chemokine levels. Together, our results indicate that B1R activation plays an important role in limiting the accumulation of Aβ in AD-like brain, likely through the regulation of activated glial cell accumulation and release of pro-inflammatory mediators. Therefore, the modulation of the receptor may represent a novel therapeutic approach for AD.
MeSH term(s)	Amyloid beta-Peptides/metabolism ; Animals ; Bradykinin B1 Receptor Antagonists ; Brain/metabolism ; Brain/pathology ; Brain/physiopathology ; Cognition ; Humans ; Inflammation/metabolism ; Inflammation/pathology ; Inflammation/physiopathology ; Mice ; Mice, Transgenic ; Nervous System/metabolism ; Nervous System/pathology ; Nervous System/physiopathology ; Neuroglia/metabolism ; Neuroglia/pathology ; Protein Processing, Post-Translational ; Receptor, Bradykinin B1/metabolism ; Up-Regulation
Chemical Substances	Amyloid beta-Peptides ; Bradykinin B1 Receptor Antagonists ; Receptor, Bradykinin B1
Language	English
Publishing date	2013-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2013.01.021
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.76: 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: Experience-dependent regulation of vesicular zinc in male and female 3xTg-AD mice.

Nakashima, Amy S / Oddo, Salvatore / Laferla, Frank M / Dyck, Richard H

Neurobiology of aging

2010 Volume 31, Issue 4, Page(s) 605–613

Abstract: In the mammalian cerebral cortex, zinc is an important modulator of synaptic transmission and conversely, plasticity. Zinc is also involved, in a sex-dependent manner, in the pathogenesis of Alzheimer's disease (AD), where substantial declines in ... ...

Abstract	In the mammalian cerebral cortex, zinc is an important modulator of synaptic transmission and conversely, plasticity. Zinc is also involved, in a sex-dependent manner, in the pathogenesis of Alzheimer's disease (AD), where substantial declines in plasticity may occur. To examine this relationship further, the regulation of vesicular zinc was examined after the induction of cortical plasticity through vibrissae plucking in male and female C57Bl/6 and 3xTg-AD mice at various age points. Female C57Bl/6 mice were found to have an elevated response compared to male C57Bl/6 mice through mid-adult ages, a sex-difference likely mediated by the differential regulation of vesicular zinc by the sex hormones. Male 3xTg-AD mice had a significantly greater zincergic response compared to C57Bl/6 mice, which is likely indicative of a compensatory mechanism utilized by the male 3xTg-AD mice to combat the decline in plasticity associated with the AD state. These results exemplify how the regulation of vesicular zinc may be a significant component in the progression of AD, especially regarding the sex-dependent element.
MeSH term(s)	Afferent Pathways/injuries ; Afferent Pathways/physiology ; Aging/metabolism ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/physiopathology ; Animals ; Denervation/adverse effects ; Disease Progression ; Female ; Gonadal Steroid Hormones/metabolism ; Learning/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuronal Plasticity/physiology ; Sex Characteristics ; Somatosensory Cortex/metabolism ; Somatosensory Cortex/physiopathology ; Transport Vesicles/metabolism ; Vibrissae/injuries ; Vibrissae/physiology ; Zinc/metabolism
Chemical Substances	Gonadal Steroid Hormones ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2010-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2008.05.028
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1685: 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)
Zs.MG 10: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Characterization of the 3xTg-AD mouse model of Alzheimer's disease: part 2. Behavioral and cognitive changes.

Sterniczuk, Roxanne / Antle, Michael C / Laferla, Frank M / Dyck, Richard H

Brain research

2010 Volume 1348, Page(s) 149–155

Abstract: Alzheimer's disease (AD) is characterized by distinct behavioral and cognitive deficits that differ from those observed in normal aging. Transgenic models of AD are a promising tool in understanding the underlying mechanisms and cause of disease. The ... ...

Abstract	Alzheimer's disease (AD) is characterized by distinct behavioral and cognitive deficits that differ from those observed in normal aging. Transgenic models of AD are a promising tool in understanding the underlying mechanisms and cause of disease. The triple-transgenic mouse model of AD (3xTg-AD) is the only model to exhibit both Abeta and tau pathology that is characteristic of the human form. The present study characterized the performance of 3xTg-AD mice on several tasks measuring behavioral and cognitive ability. Aged 3xTg-AD females exhibited a higher level of fear and anxiety demonstrated by increased restlessness, startle responses, and freezing behaviors. No differences were observed in muscle strength and visuo-motor coordination. Understanding the behavioral manifestations that occur in this model of AD may aid in the early diagnosis and appropriate treatment of AD symptomology.
MeSH term(s)	Alzheimer Disease/complications ; Alzheimer Disease/genetics ; Amyloid Precursor Protein Secretases ; Amyloid beta-Protein Precursor ; Animals ; Animals, Genetically Modified ; Avoidance Learning/physiology ; Behavioral Symptoms/etiology ; Behavioral Symptoms/genetics ; Cognition Disorders/etiology ; Cognition Disorders/genetics ; Disease Models, Animal ; Exploratory Behavior/physiology ; Female ; Humans ; Male ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL ; Motor Activity/genetics ; Neurologic Examination ; Presenilin-1 ; Psychomotor Performance/physiology ; Reaction Time/genetics ; Statistics, Nonparametric ; Time Factors
Chemical Substances	Amyloid beta-Protein Precursor ; PSEN1 protein, human ; Presenilin-1 ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2010-08-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2010.06.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 161: 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

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Characterization of the 3xTg-AD mouse model of Alzheimer's disease: part 1. Circadian changes.

Sterniczuk, Roxanne / Dyck, Richard H / Laferla, Frank M / Antle, Michael C

Brain research

2010 Volume 1348, Page(s) 139–148

Abstract: Circadian disturbances, including a fragmented sleep-wake pattern and sundowning, are commonly reported early in the progression of Alzheimer's disease (AD). These changes are distinctly different from those observed in non-pathological aging. Transgenic ...

Abstract	Circadian disturbances, including a fragmented sleep-wake pattern and sundowning, are commonly reported early in the progression of Alzheimer's disease (AD). These changes are distinctly different from those observed in non-pathological aging. Transgenic models of AD are a promising tool in understanding the underlying mechanisms and cause of disease. A novel triple-transgenic model of AD, 3xTg-AD, is the only model to exhibit both Abeta and tau pathology, and mimic human AD. The present study characterized changes pertaining to circadian rhythmicity that occur prior to and post-AD pathology. Both male and female 3xTg-AD mice demonstrated alterations to their circadian pacemaker with decreased nocturnal behavior when compared to controls. Specifically, males showed greater locomotor activity during the day and shorter freerunning periods prior to the onset of AD-pathology, and females had a decrease in activity levels during their typical active phase. Both sexes did not differ in terms of their freerunning periods or photic phase shifting ability. A decrease in vasoactive intestinal polypeptide-containing and vasopressin-containing cells was observed in the suprachiasmatic nucleus of 3xTg-AD mice relative to controls. This study demonstrates that abnormalities in circadian rhythmicity in 3xTg-AD mice precede expected AD pathology. This suggests that human studies may wish to determine if similar circadian dysfunction is predictive of early-onset AD.
MeSH term(s)	Age Factors ; Alzheimer Disease/complications ; Alzheimer Disease/genetics ; Amyloid Precursor Protein Secretases ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor ; Analysis of Variance ; Animals ; Animals, Genetically Modified ; Chronobiology Disorders/etiology ; Chronobiology Disorders/genetics ; Chronobiology Disorders/pathology ; Disease Models, Animal ; Female ; Gene Expression Regulation/genetics ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity/genetics ; Nerve Growth Factors/metabolism ; Presenilin-1 ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins/metabolism ; Suprachiasmatic Nucleus/metabolism ; Vasoactive Intestinal Peptide/metabolism ; Vasopressins/metabolism
Chemical Substances	Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Nerve Growth Factors ; PSEN1 protein, human ; Presenilin-1 ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; Vasopressins (11000-17-2) ; Vasoactive Intestinal Peptide (37221-79-7) ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2010-08-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2010.05.013
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 161: 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

Details ▾
- See ZB MED holdings
- Order with fees

Article: Pathways by which Abeta facilitates tau pathology.

Blurton-Jones, Mathew / Laferla, Frank M

Current Alzheimer research

2006 Volume 3, Issue 5, Page(s) 437–448

Abstract: Since the initial description one hundred years ago by Dr. Alois Alzheimer, the disorder that bears his name has been characterized by the occurrence of two brain lesions: amyloid plaques and neurofibrillary tangles (NFTs). Yet the precise relationship ... ...

Abstract	Since the initial description one hundred years ago by Dr. Alois Alzheimer, the disorder that bears his name has been characterized by the occurrence of two brain lesions: amyloid plaques and neurofibrillary tangles (NFTs). Yet the precise relationship between beta-amyloid (Abeta) and tau, the two proteins that accumulate within these lesions, has proven elusive. Today, a growing body of work supports the notion that Abeta may directly or indirectly interact with tau to accelerate NFT formation. Here we review recent evidence that Abeta can adversely affect distinct molecular and cellular pathways, thereby facilitating tau phosphorylation, aggregation, mis-localization, and accumulation. Studies are presented that support four putative mechanisms by which Abeta may facilitate the development of tau pathology. A great deal of work suggests that Abeta may drive tau pathology by activating specific kinases, providing a straightforward mechanism by which Abeta may enhance tau hyperphosphorylation and NFT formation. In the AD brain, Abeta also triggers a massive inflammatory response and pro-inflammatory cytokines can in turn indirectly modulate tau phosphorylation. Mounting evidence also suggests that Abeta may inhibit tau degradation via the proteasome. Lastly, Abeta and tau may indirectly interact at the level of axonal transport and evidence is presented for two possible scenarios by which axonal transport deficits may play a role. We propose that the four putative mechanisms described in this review likely mediate the interactions between Abeta and tau, thereby leading to the development of AD neurodegeneration.
MeSH term(s)	Alzheimer Disease/history ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/physiology ; Animals ; Axonal Transport/physiology ; Enzyme Activation ; History, 20th Century ; History, 21st Century ; Humans ; Inflammation/chemically induced ; Inflammation/metabolism ; Neurofibrillary Tangles/metabolism ; Neurofibrillary Tangles/pathology ; Plaque, Amyloid/metabolism ; Plaque, Amyloid/pathology ; Proteasome Endopeptidase Complex/metabolism ; Signal Transduction/physiology ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; tau Proteins ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2006-11-15
Publishing country	United Arab Emirates
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2205170-3
ISSN	1567-2050
ISSN	1567-2050
DOI	10.2174/156720506779025242
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6235: 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: Genetic ablation of tau mitigates cognitive impairment induced by type 1 diabetes.

Abbondante, Serena / Baglietto-Vargas, David / Rodriguez-Ortiz, Carlos J / Estrada-Hernandez, Tatiana / Medeiros, Rodrigo / Laferla, Frank M

The American journal of pathology

2014 Volume 184, Issue 3, Page(s) 819–826

Abstract: Patients affected by diabetes show an increased risk of developing Alzheimer disease (AD). Similarly, patients with AD show impaired insulin function and glucose metabolism. However, the underlying molecular mechanisms connecting these two disorders are ... ...

Abstract	Patients affected by diabetes show an increased risk of developing Alzheimer disease (AD). Similarly, patients with AD show impaired insulin function and glucose metabolism. However, the underlying molecular mechanisms connecting these two disorders are still not well understood. Herein, we investigated the microtubule-associated protein tau as a new link between AD and diabetes. To determine whether diabetes causes cognitive decline by a tau-dependent mechanism, we treated non-transgenic (Ntg) and tau-knockout mice with streptozotocin, causing type 1 diabetes-like disease (T1D). Interestingly, although induction of T1D in Ntg mice led to cellular and behavioral deficits, it did not do so in tau-knockout mice. Thus, data suggest that tau is a fundamental mediator of the induction of cognitive impairments in T1D. Tau dysregulation, which causes a reduction in synaptic protein levels, may be responsible for the cognitive decline observed in Ntg streptozotocin-treated mice. Concomitantly, we demonstrate the novel finding that depletion of endogenous tau mitigates behavioral impairment and synaptic deficits induced in T1D-like mice. Overall, our data reveal that tau is a key molecular factor responsible for the induction of cognitive deficits observed in T1D and represents a potential therapeutic target for diabetes and patients with AD.
MeSH term(s)	Alzheimer Disease/etiology ; Animals ; Cognition ; Cognition Disorders/etiology ; Diabetes Mellitus, Type 1/complications ; Disease Models, Animal ; Female ; Humans ; Insulin/metabolism ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Streptozocin/metabolism ; tau Proteins/genetics ; tau Proteins/metabolism
Chemical Substances	Insulin ; tau Proteins ; Streptozocin (5W494URQ81)
Language	English
Publishing date	2014-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2013.11.021
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.76: 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: Oligemic hypoperfusion differentially affects tau and amyloid-{beta}.

Koike, Maya A / Green, Kim N / Blurton-Jones, Mathew / Laferla, Frank M

The American journal of pathology

2010 Volume 177, Issue 1, Page(s) 300–310

Abstract: Decreased blood flow to the brain in humans is associated with altered Alzheimer's disease (AD)-related pathology, although the underlying mechanisms by which hypoperfusion influences AD neuropathology remains unknown. To try to address this question, we ...

Abstract	Decreased blood flow to the brain in humans is associated with altered Alzheimer's disease (AD)-related pathology, although the underlying mechanisms by which hypoperfusion influences AD neuropathology remains unknown. To try to address this question, we developed an oligemic model of cerebral hypoperfusion in the 3xTg-AD mouse model of AD. We bilaterally and transiently occluded the common carotid artery and then examined the molecular and cellular pathways by which hypoperfusion influenced tau and amyloid-beta proteins. We report the novel finding that a single, mild, transient hypoperfusion insult acutely increases Abeta levels by enhancing beta-secretase protein expression. In contrast, transient hypoperfusion markedly decreases total tau levels, coincident with activation of macroautophagy and ubiquitin-proteosome pathways. Furthermore, we find that oligemia results in a significant increase specifically in tau phosphorylated at serine(212) and threonine(214), a tau epitope associated with paired helical filaments in AD patients. Despite the mild and transient nature of this hypoperfusion injury, the pattern of decreased total tau, altered phosphorylated tau, and increased amyloid-beta persisted for several weeks postoligemia. Our study indicates that a single, mild, cerebral hypoperfusion event produces profound and long lasting effects on both tau and amyloid-beta. This finding may have implications for the pathogenesis of AD, as it indicates for the first time that total tau and amyloid-beta are differentially impacted by mild hypoperfusion.
MeSH term(s)	Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Biomarkers/metabolism ; Brain/anatomy & histology ; Brain/metabolism ; Brain/pathology ; Brain Ischemia/metabolism ; Brain Ischemia/pathology ; Cerebrovascular Circulation/physiology ; Humans ; Lysosomes/metabolism ; Mice ; Mice, Transgenic ; Regional Blood Flow/physiology ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Protein Precursor ; Biomarkers ; tau Proteins
Language	English
Publishing date	2010-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.2353/ajpath.2010.090750
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.76: 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 ▾

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

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

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

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