The Experts below are selected from a list of 3792 Experts worldwide ranked by ideXlab platform
Jari Koistinaho - One of the best experts on this subject based on the ideXlab platform.
-
generation of a human induced pluripotent stem cell line ll008 1 4 from a familial alzheimer s disease patient carrying a double km670 671nl Swedish Mutation in app gene
2018Co-Authors: Minna Oksanen, Ida Hyötyläinen, Jenni Voutilainen, Katja A. Puttonen, Riikka H. Hämäläinen, Caroline Graff, Šárka Lehtonen, Jari KoistinahoAbstract:A double Mutation (KM670/671NL) in amyloid precursor protein gene (APP) is causative for familial Alzheimer's disease and has been shown to increase the total Aβ burden. Here we report the generation and characterization of an iPSC line from a fAD patient carrying APP KM670/671NL. The generated iPSCs retained the Mutation, expressed pluripotency markers, showed a normal karyotype and differentiated into all three germ layers. This iPSC line can be used, for example, in disease modeling and mechanistic studies. Resource table.
-
Generation of a human induced pluripotent stem cell line (LL008 1.4) from a familial Alzheimer's disease patient carrying a double KM670/671NL (Swedish) Mutation in APP gene
2018Co-Authors: Minna Oksanen, Ida Hyötyläinen, Jenni Voutilainen, Katja A. Puttonen, Riikka H. Hämäläinen, Caroline Graff, Šárka Lehtonen, Jari KoistinahoAbstract:A double Mutation (KM670/671NL) in amyloid precursor protein gene (APP) is causative for familial Alzheimer's disease and has been shown to increase the total Aβ burden. Here we report the generation and characterization of an iPSC line from a fAD patient carrying APP KM670/671NL. The generated iPSCs retained the Mutation, expressed pluripotency markers, showed a normal karyotype and differentiated into all three germ layers. This iPSC line can be used, for example, in disease modeling and mechanistic studies.Resource table.Unlabelled TableUnique stem cell line identifierUEFi002-AAlternative name(s) of stem cell lineLL008 1.4InstitutionA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandContact information of distributorProf. Jari Koistinaho(jari.koistinaho@uef.fi; jari.koistinaho@helsinki.fi)Type of cell lineiPSCOriginHumanAdditional origin infoAge: 58Sex: FemaleEthnicity: ScandinavianCell SourceSkin fibroblastsClonalityClonalMethod of reprogrammingSendai virus carrying OCT3/4, SOX2, KLF4 and c-MYC(CytoTune 1.0)Genetic ModificationNoType of ModificationN/AAssociated diseaseFamilial Alzheimer's diseaseGene/locusAPP (MIM # 104760) located on the long arm of chromosome 21 at position 21q21.3; 27,269,939 G > T, 27269938 A > C (rs63751263, rs63750445)Method of modificationN/AName of transgene or resistanceN/AInducible/constitutive systemN/ADate archived/stock dateMarch 2016Cell line repository/bankN/AEthical approvalEthical license number 2017/834–31/1 (The ethical review board of Karolinska Institutet/Karolinska University Hospital
Reinhard Schliebs - One of the best experts on this subject based on the ideXlab platform.
-
arsenic affects expression and processing of amyloid precursor protein app in primary neuronal cells overexpressing the Swedish Mutation of human app
2011Co-Authors: Sergio Zarazua, Susanne Burger, Juan Manuel Delgado, Maria E Jimenezcapdeville, Reinhard SchliebsAbstract:Abstract Arsenic poisoning due to contaminated water and soil, mining waste, glass manufacture, select agrochemicals, as well as sea food, affects millions of people world wide. Recently, an involvement of arsenic in Alzheimer's disease (AD) has been hypothesized ( Gong and O’Bryant, 2010 ). The present study stresses the hypothesis whether sodium arsenite, and its main metabolite, dimethylarsinic acid (DMA), may affect expression and processing of the amyloid precursor protein (APP), using the cholinergic cell line SN56.B5.G4 and primary neuronal cells overexpressing the Swedish Mutation of APP, as experimental approaches. Exposure of cholinergic SN56.B5.G4 cells with either sodium arsenite or DMA decreased cell viability in a concentration- and exposure-time dependent manner, and affected the activities of the cholinergic enzymes acetylcholinesterase and choline acetyltransferase. Both sodium arsenite and DMA exposure of SN56.B5.G4 cells resulted in enhanced level of APP, and sAPP in the membrane and cytosolic fractions, respectively. To reveal any effect of arsenic on APP processing, the amounts of APP cleavage products, sAPPβ, and β-amyloid (Aβ) peptides, released into the culture medium of primary neuronal cells derived from transgenic Tg2576 mice, were assessed by ELISA. Following exposure of neuronal cells by sodium arsenite for 12 h, the membrane-bound APP level was enhanced, the amount of sAPPβ released into the culture medium was slightly higher, while the levels of Aβ peptides in the culture medium were considerably lower as compared to that assayed in the absence of any drug. The sodium arsenite-induced reduction of Aβ formation suggests an inhibition of the APP γ-cleavage step by arsenite. In contrast, DMA exposure of neuronal cells considerably increased formation of Aβ and sAPPβ, accompanied by enhanced membrane APP level. The DMA-induced changes in APP processing may be the result of the enhanced APP expression. Alternatively, increased Aβ production may also be due to stimulation of caspase activity by arsenic compounds, or failure in Aβ degradation. In summary, the present report clearly demonstrates that sodium arsenite and DMA affect processing of APP in vitro.
-
Impairment of cholinergic neurotransmission in adult and aged transgenic Tg2576 mouse brain expressing the Swedish Mutation of human beta-amyloid precursor protein.
2002Co-Authors: Jenny Apelt, Ashok Kumar, Reinhard SchliebsAbstract:To address the question of whether beta-amyloid peptides also affect cholinergic neurotransmission in vivo, brain tissue from transgenic Tg2576 mice with Alzheimer plaque pathology at ages ranging from 7 to 24 months were examined by immuno- and histochemical staining for choline acetyltransferase (ChAT) and acetycholinesterase (AChE), by assaying cholinergic enzyme activities and high-affinity choline uptake as well muscarinic and nicotinic cholinergic receptor binding levels by quantitative autoradiography. Cortical and hippocampal activities of AChE and ChAT were not different between transgenic mice and non-transgenic littermates regardless of the postnatal ages examined. However, high-affinity choline uptake was reduced in the hippocampus of 21-month-old transgenic mice. In brains of 8-month-old transgenic mice which do not yet demonstrate cortical beta-amyloids, reduced binding levels of cortical and hippocampal M1-muscarinic cholinergic receptors were observed, which were still reduced in 17-month-old transgenic mouse brains with high plaque load as compared to non-transgenic littermates. M2-muscarinic cholinergic receptor binding was hardly affected in brains from 8-month-old transgenic mice, but in 17-month-old transgenic mice reduced cortical and hippocampal binding levels were observed as compared to non-transgenic controls. Decreased cortical nicotinic cholinergic receptor binding was detected in 17-month-old transgenic mice. The development of changes in cholinergic synaptic markers in transgenic Tg2576 mouse brain before the onset of progressive plaque deposition provides in vivo evidence of a modulatory role of soluble beta-amyloid on cholinergic neurotransmission and may be referred to the deficits in learning and memory also observed in these mice before significant plaque load.
-
Impairment of cholinergic neurotransmission in adult and aged transgenic Tg2576 mouse brain expressing the Swedish Mutation of human β-amyloid precursor protein
2002Co-Authors: Jenny Apelt, Ashok Kumar, Reinhard SchliebsAbstract:Abstract To address the question of whether β-amyloid peptides also affect cholinergic neurotransmission in vivo, brain tissue from transgenic Tg2576 mice with Alzheimer plaque pathology at ages ranging from 7 to 24 months were examined by immuno- and histochemical staining for choline acetyltransferase (ChAT) and acetycholinesterase (AChE), by assaying cholinergic enzyme activities and high-affinity choline uptake as well muscarinic and nicotinic cholinergic receptor binding levels by quantitative autoradiography. Cortical and hippocampal activities of AChE and ChAT were not different between transgenic mice and non-transgenic littermates regardless of the postnatal ages examined. However, high-affinity choline uptake was reduced in the hippocampus of 21-month-old transgenic mice. In brains of 8-month-old transgenic mice which do not yet demonstrate cortical β-amyloids, reduced binding levels of cortical and hippocampal M1-muscarinic cholinergic receptors were observed, which were still reduced in 17-month-old transgenic mouse brains with high plaque load as compared to non-transgenic littermates. M2-muscarinic cholinergic receptor binding was hardly affected in brains from 8-month-old transgenic mice, but in 17-month-old transgenic mice reduced cortical and hippocampal binding levels were observed as compared to non-transgenic controls. Decreased cortical nicotinic cholinergic receptor binding was detected in 17-month-old transgenic mice. The development of changes in cholinergic synaptic markers in transgenic Tg2576 mouse brain before the onset of progressive plaque deposition provides in vivo evidence of a modulatory role of soluble β-amyloid on cholinergic neurotransmission and may be referred to the deficits in learning and memory also observed in these mice before significant plaque load.
-
Expression of β-secretase mRNA in transgenic Tg2576 mouse brain with Alzheimer plaque pathology
2000Co-Authors: Marina Bigl, Jenny Apelt, E.a Luschekina, C. Lange-dohna, Steffen Roßner, Reinhard SchliebsAbstract:On the basis of the recent cloning of the β-secretase, the beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE), (Science, 286 (1999) 735), digoxigenin-labelled riboprobes were generated to localize the cellular expression pattern of BACE mRNA in brain sections of transgenic Tg2576 mice, overexpressing the Swedish Mutation of the APP695 isoform. Non-radioactive in situ hybridization in combination with immunohistochemistry to identify the cell types and β-amyloid deposits revealed strong BACE mRNA hybridization signals in neurons of the cerebral cortex, hippocampal formation, thalamus and cholinergic basal forebrain nuclei, while astrocytes did not display any labeling. Neurons surrounding β-amyloid deposits did not demonstrate altered expression level of BACE mRNA as compared to neurons in cortical areas that are free of β-amyloid deposits, and the regional expression pattern of BACE mRNA did not correlate with the distribution of β-amyloid deposits. These data suggest that high level of expression of BACE mRNA is not necessarily related to enhanced deposition of β-amyloid plaques. To elucidate those factors that contribute to β-amyloid plaque deposition in a particular region, the transgenic Tg2576 mouse may represent an appropriate tool.
Caroline Graff - One of the best experts on this subject based on the ideXlab platform.
-
generation of a human induced pluripotent stem cell line ll008 1 4 from a familial alzheimer s disease patient carrying a double km670 671nl Swedish Mutation in app gene
2018Co-Authors: Minna Oksanen, Ida Hyötyläinen, Jenni Voutilainen, Katja A. Puttonen, Riikka H. Hämäläinen, Caroline Graff, Šárka Lehtonen, Jari KoistinahoAbstract:A double Mutation (KM670/671NL) in amyloid precursor protein gene (APP) is causative for familial Alzheimer's disease and has been shown to increase the total Aβ burden. Here we report the generation and characterization of an iPSC line from a fAD patient carrying APP KM670/671NL. The generated iPSCs retained the Mutation, expressed pluripotency markers, showed a normal karyotype and differentiated into all three germ layers. This iPSC line can be used, for example, in disease modeling and mechanistic studies. Resource table.
-
Generation of a human induced pluripotent stem cell line (LL008 1.4) from a familial Alzheimer's disease patient carrying a double KM670/671NL (Swedish) Mutation in APP gene
2018Co-Authors: Minna Oksanen, Ida Hyötyläinen, Jenni Voutilainen, Katja A. Puttonen, Riikka H. Hämäläinen, Caroline Graff, Šárka Lehtonen, Jari KoistinahoAbstract:A double Mutation (KM670/671NL) in amyloid precursor protein gene (APP) is causative for familial Alzheimer's disease and has been shown to increase the total Aβ burden. Here we report the generation and characterization of an iPSC line from a fAD patient carrying APP KM670/671NL. The generated iPSCs retained the Mutation, expressed pluripotency markers, showed a normal karyotype and differentiated into all three germ layers. This iPSC line can be used, for example, in disease modeling and mechanistic studies.Resource table.Unlabelled TableUnique stem cell line identifierUEFi002-AAlternative name(s) of stem cell lineLL008 1.4InstitutionA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandContact information of distributorProf. Jari Koistinaho(jari.koistinaho@uef.fi; jari.koistinaho@helsinki.fi)Type of cell lineiPSCOriginHumanAdditional origin infoAge: 58Sex: FemaleEthnicity: ScandinavianCell SourceSkin fibroblastsClonalityClonalMethod of reprogrammingSendai virus carrying OCT3/4, SOX2, KLF4 and c-MYC(CytoTune 1.0)Genetic ModificationNoType of ModificationN/AAssociated diseaseFamilial Alzheimer's diseaseGene/locusAPP (MIM # 104760) located on the long arm of chromosome 21 at position 21q21.3; 27,269,939 G > T, 27269938 A > C (rs63751263, rs63750445)Method of modificationN/AName of transgene or resistanceN/AInducible/constitutive systemN/ADate archived/stock dateMarch 2016Cell line repository/bankN/AEthical approvalEthical license number 2017/834–31/1 (The ethical review board of Karolinska Institutet/Karolinska University Hospital
-
increased epileptiform eeg activity and decreased seizure threshold in arctic app transgenic mouse model of alzheimer s disease
2016Co-Authors: Sofya Ziyatdinova, Caroline Graff, Annica Ronnback, Kestutis Gurevicius, Diana Miszczuk, Bengt Winblad, Asla Pitkanen, Heikki TanilaAbstract:Several Alzheimer model mice carrying transgenic amyloid precursor protein (APP) with the Swedish Mutation have been reported to exhibit spontaneous seizures and/or increased epileptiform EEG activity. The primary cause for the epilepsy phenotype is still under debate. In contrast to mice with APPswe Mutation that develop extracellular amyloid plaques, mice with APP Arctic Mutation (E693G) have no bias toward β-secretase cleavage and display intracellular amyloid deposits but not plaques. We conducted a systematic long-term video-EEG recording in three two-week sessions on 21 APParc and 11 wild-type control mice between 3.5 and 8 months of age. Spontaneous seizures were not detected more often in APParc mice than in their wild-type control mice. Long (1 – 5 s) epileptiform discharges were occasionally detected in both APParc and wild-type mice, but short (0.5 – <1 s) epileptiform discharges were more common in APParc mice than in wild-types. However, they were far less frequent than in 6 APPswe/PS1dE9 mice recorded in parallel. In pentylenetetrazole test for seizure susceptibility, APParc mice displayed a shorter latency to sharp-wave discharges than wildtype mice but no increase in seizure duration. These data speak for a relatively mild epilepsy phenotype in APParc mice compared to APPswe mice despite even higher extent of APP overexpression. Thus extracellular amyloid plaques or increased β-secretase cleavage products appear important for the epilepsy phenotype in APPswe mice.
-
autophagic and lysosomal defects in human tauopathies analysis of post mortem brain from patients with familial alzheimer disease corticobasal degeneration and progressive supranuclear palsy
2016Co-Authors: Antonio Piras, Caroline Graff, Ludovic Collin, Fiona Gruninger, Annica RonnbackAbstract:Introduction The accumulation of insoluble proteins within neurons and glia cells is a pathological hallmark of several neurodegenerative diseases. Abnormal aggregation of the microtubule-associated protein tau characterizes the neuropathology of tauopathies, such as Alzheimer disease (AD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). An impairment of the lysosomal degradation pathway called macroautophagy, hereafter referred to as autophagy, could contribute to the accumulation of aggregated proteins. The role of autophagy in neurodegeneration has been intensively studied in the context of AD but there are few studies in other tauopathies and it is not known if defects in autophagy is a general feature of tauopathies. In the present study, we analysed autophagic and lysosomal markers in human post-mortem brain samples from patients with early-onset familial AD (FAD) with the APP Swedish Mutation (APPswe), CBD and PSP and control individuals.
Robert Lalonde - One of the best experts on this subject based on the ideXlab platform.
-
spatial learning and exploration of environmental stimuli in 24 month old female app23 transgenic mice with the Swedish Mutation
2004Co-Authors: M Dumont, Matthias Staufenbiel, C Strazielle, Robert LalondeAbstract:Transgenic mice overexpressing the βAPP gene with the Swedish Mutation under the control of the murine thy1 promoter show Alzheimer-like characteristics such as Aβ plaques in cerebral cortex and vessel walls. By comparison to age-matched non-transgenic controls, 2-year-old female APP23 transgenic mice crossed more segments in the open-field and had a higher number of fast ambulatory and stereotyped movements in a photocell activity chamber. In addition, APP23 mice entered more often and spent more time in the open arms of the elevated plus-maze. The acquisition of place learning in the Morris water maze was impaired in APP23 transgenic mice, but not in probe and visible platform subtasks. These results indicate that hyperactivity and impaired learning abilities characterize this mouse model of Alzheimer's disease and cerebral angiopathy.
-
regional brain cytochrome oxidase activity in β amyloid precursor protein transgenic mice with the Swedish Mutation
2003Co-Authors: C Strazielle, C Sturchlerpierrat, M Staufenbiel, Robert LalondeAbstract:Abstract Cytochrome oxidase activity was examined in a transgenic mouse model of Alzheimer’s disease with overexpression of the 751 amino acid isoform of β-amyloid precursor protein with the Swedish Mutation under control of the murine thy-1 promoter. The neuritic plaques, abundantly localized in the hippocampus and anterior neocortical areas, showed a core devoid of enzymatic activity surrounded by higher cytochrome oxidase activity at the sites of the dystrophic neurites and activated glial cells. Quantitative measures, taken only in the healthy-appearing regional areas without neuritic plaques, were higher in numerous limbic and non-limbic regions of transgenic mice in comparison with controls. Enzymatic activity was higher in the dentate gyrus and CA2–CA3 region of the hippocampus, the anterior cingulate and primary visual cortex, two olfactory structures, the ventral part of the neostriatum, the parafascicularis nucleus of the thalamus, and the subthalamic nucleus. Brainstem regions anatomically related with altered forebrain regions were more heavily labeled as well, including the substantia nigra, the periaqueductal gray, the superior colliculus, the medial raphe, the locus coeruleus and the adjacent parabrachial nucleus, as well as the pontine nuclei, red nucleus, and trigeminal motor nucleus. Functional brain organization is discussed in the context of Alzheimer’s disease. Although hypometabolism is generally observed in this pathology, the increased cytochrome oxidase activity obtained in these transgenic mice can be the result of a functional compensation on the surviving neurons, or of an early mitochondrial alteration related to increased oxidative damage.
-
spatial learning exploration anxiety and motor coordination in female app23 transgenic mice with the Swedish Mutation
2002Co-Authors: Robert Lalonde, M Dumont, Matthias Staufenbiel, C Sturchlerpierrat, C StrazielleAbstract:Abstract Transgenic mice overexpressing the βAPP gene with the Swedish Mutation under the control of the murine thy-1 promoter show Alzheimer-like characteristics including the accumulation of Aβ protein in the cerebral cortex. Female 16-month-old APP23 transgenic mice were compared to age-matched non-transgenic mice in behavioral tests measuring spatial learning, exploration of environmental stimuli, anxiety, and motor coordination. APP23 transgenic mice had fewer fast ambulatory movements, either fast or slow stereotypy movements, and slow rears in a photocell activity chamber. The acquisition of spatial learning in the Morris water maze was impaired in APP23 transgenic mice, but not during the probe test or while swimming towards a visible platform. Neither were there intergroup differences in tests of anxiety or motor coordination. These results indicate that a learning deficit and hypoactivity, concordant with the early stages of Alzheimer’s disease, characterize this mouse model with Aβ accumulation.
Matthias Staufenbiel - One of the best experts on this subject based on the ideXlab platform.
-
changes in amyloid β and tau in the cerebrospinal fluid of transgenic mice overexpressing amyloid precursor protein
2013Co-Authors: Matthias Staufenbiel, Julia Reichwald, Luis F Maia, Stephan A Kaeser, Michael Hruscha, Peter Martus, Mathias JuckerAbstract:Altered concentrations of amyloid-β (Aβ) peptide and Tau protein in the cerebrospinal fluid (CSF) are thought to be predictive markers for Alzheimer's disease (AD). Transgenic mice overexpressing human amyloid precursor protein (APP) have been used to model Aβ pathology, but concomitant changes in Aβ and Tau in CSF have been less well studied. We measured Aβ and Tau in the brains and CSF of two well-characterized transgenic mouse models of AD: one expressing human APP carrying the Swedish Mutation (APP23) and the other expressing mutant human APP and mutant human presenilin-1 (APPPS1). Both mouse models exhibit Aβ deposition in the brain, but with different onset and progression trajectories. We found an age-related 50 to 80% decrease in Aβ42 peptide in mouse CSF and a smaller decrease in Aβ40, both inversely correlated with the brain Aβ load. Surprisingly, the same mice showed a threefold increase in total endogenous murine Tau in CSF at the stages when Aβ pathology became prominent. The results mirror the temporal sequence and magnitude of Aβ and Tau changes in the CSF of patients with sporadic and dominantly inherited AD. This observation indicates that APP transgenic mice may be useful as a translational tool for predicting changes in Aβ and Tau markers in the CSF of AD patients. These findings also suggest that APP transgenic mouse models may be useful in the search for new disease markers for AD.
-
the Swedish app Mutation alters the effect of genetically reduced bace1 expression on the app processing
2011Co-Authors: Sabine Rabe, Julia Reichwald, Domenico Ammaturo, Bart De Strooper, Paul Saftig, Ulf Neumann, Matthias StaufenbielAbstract:J. Neurochem. (2011) 119, 231–239. Abstract Inhibition of β-secretase (BACE1) is a key therapeutic approach in Alzheimer’s disease (AD), as BACE1 initiates amyloid-β (Aβ) cleavage from the β-amyloid precursor protein (APP). As Aβ reductions in mice lacking one BACE1 allele diverged considerably between studies we investigated the effect of BACE1 knock-out in more detail. With both BACE1 alleles the Swedish Mutation (APP23 mice) increased APP processing and shifted it towards the β-secretase pathway as compared with non-mutated APP expressed at a similar level (APP51/16 mice). This effect was much smaller then observed in cell culture. An about 50% decrease in BACE1 enzyme activity resulted in a sub-proportional Aβ reduction with the Swedish Mutation (−20%) and even less for non-mutated APP (−16%). In wild-type mice, the Aβ reduction may be even further diminished. Other metabolites of the β-secretase pathway decreased accordingly while the alternative α-secretase pathway increased. Complete BACE1 deletion strongly enhanced these changes. The remaining Aβ signal also described by others can be explained by assay cross-reactivity with other APP metabolites supporting BACE1 as the major β-secretase. Our data indicate that BACE1 is in excess over APP at the cleavage site(s). Alterations in APP expression or substrate properties, therefore, quantitatively change its cleavage and Aβ generation.
-
spatial learning and exploration of environmental stimuli in 24 month old female app23 transgenic mice with the Swedish Mutation
2004Co-Authors: M Dumont, Matthias Staufenbiel, C Strazielle, Robert LalondeAbstract:Transgenic mice overexpressing the βAPP gene with the Swedish Mutation under the control of the murine thy1 promoter show Alzheimer-like characteristics such as Aβ plaques in cerebral cortex and vessel walls. By comparison to age-matched non-transgenic controls, 2-year-old female APP23 transgenic mice crossed more segments in the open-field and had a higher number of fast ambulatory and stereotyped movements in a photocell activity chamber. In addition, APP23 mice entered more often and spent more time in the open arms of the elevated plus-maze. The acquisition of place learning in the Morris water maze was impaired in APP23 transgenic mice, but not in probe and visible platform subtasks. These results indicate that hyperactivity and impaired learning abilities characterize this mouse model of Alzheimer's disease and cerebral angiopathy.
-
spatial learning exploration anxiety and motor coordination in female app23 transgenic mice with the Swedish Mutation
2002Co-Authors: Robert Lalonde, M Dumont, Matthias Staufenbiel, C Sturchlerpierrat, C StrazielleAbstract:Abstract Transgenic mice overexpressing the βAPP gene with the Swedish Mutation under the control of the murine thy-1 promoter show Alzheimer-like characteristics including the accumulation of Aβ protein in the cerebral cortex. Female 16-month-old APP23 transgenic mice were compared to age-matched non-transgenic mice in behavioral tests measuring spatial learning, exploration of environmental stimuli, anxiety, and motor coordination. APP23 transgenic mice had fewer fast ambulatory movements, either fast or slow stereotypy movements, and slow rears in a photocell activity chamber. The acquisition of spatial learning in the Morris water maze was impaired in APP23 transgenic mice, but not during the probe test or while swimming towards a visible platform. Neither were there intergroup differences in tests of anxiety or motor coordination. These results indicate that a learning deficit and hypoactivity, concordant with the early stages of Alzheimer’s disease, characterize this mouse model with Aβ accumulation.
