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Adult course in dynamin 2 dominant centronuclear myopathy with neonatal onset.

https://arctichealth.org/en/permalink/ahliterature98718
Source
Neuromuscul Disord. 2010 Jan;20(1):53-6
Publication Type
Article
Date
Jan-2010
Author
Atle Melberg
Christine Kretz
Hannu Kalimo
Carina Wallgren-Pettersson
Anne Toussaint
Johann Böhm
Erik Stålberg
Jocelyn Laporte
Author Affiliation
Department of Neuroscience, Neurology, University Hospital, Uppsala University, Uppsala, Sweden.
Source
Neuromuscul Disord. 2010 Jan;20(1):53-6
Date
Jan-2010
Language
English
Publication Type
Article
Keywords
Adult
Age of Onset
Amino Acid Substitution
Disease Progression
Dynamin II - genetics
Family
Female
Humans
Infant
Middle Aged
Muscle, Skeletal - pathology - physiopathology
Myopathies, Structural, Congenital - genetics - pathology - physiopathology
Phenotype
Sequence Analysis, DNA
Sweden
Abstract
We report a family with autosomal dominant centronuclear (myotubular) myopathy caused by a novel mutation, p.A618D, in dynamin 2 (DNM2). The 64-year-old mother and 26-year-old daughter had neonatal onset with hypotonia and weak suckling, followed by improvement, then slowly progressive muscle weakness and respiratory restriction. Muscle biopsy showed radial sarcoplasmic strands around the frequent central nuclei. Electrophysiology revealed predominantly myopathic patterns without peripheral nerve involvement. Centronuclear myopathy with neonatal onset caused by a DNM2 mutation in the C-terminal part of the pleckstrin homology domain may have a favorable prognosis and follow a course similar to adult-onset centronuclear myopathy. We advise respiratory follow-up in these patients.
PubMed ID
19932619 View in PubMed
Less detail

alpha-Synuclein pathology in the spinal cord autonomic nuclei associates with alpha-synuclein pathology in the brain: a population-based Vantaa 85+ study.

https://arctichealth.org/en/permalink/ahliterature146471
Source
Acta Neuropathol. 2010 Jun;119(6):715-22
Publication Type
Article
Date
Jun-2010
Author
Minna Oinas
Anders Paetau
Liisa Myllykangas
Irma-Leena Notkola
Hannu Kalimo
Tuomo Polvikoski
Author Affiliation
Department of Pathology, Helsinki University Central Hospital,University of Helsinki, P.O. Box 21, Haartmaninkatu 3, 00014 Helsinki, Finland. minna.oinas@helsinki.fi
Source
Acta Neuropathol. 2010 Jun;119(6):715-22
Date
Jun-2010
Language
English
Publication Type
Article
Keywords
Age Factors
Aged, 80 and over
Autonomic Nervous System - metabolism - pathology
Brain - metabolism - pathology
Brain Diseases - metabolism - pathology
Cohort Studies
Female
Finland
Humans
Immunohistochemistry
Male
Neuropil - metabolism - pathology
Sacrococcygeal Region
Severity of Illness Index
Spinal Cord - metabolism - pathology
Spinal Cord Diseases - metabolism - pathology
Thoracic Vertebrae
alpha-Synuclein - metabolism
Abstract
In most subjects with Parkinson's disease and dementia with Lewy bodies, alpha-synuclein (alphaS) immunoreactive pathology is found not only in the brain but also in the autonomic nuclei of the spinal cord. However, neither has the temporal course of alphaS pathology in the spinal cord in relation to the brain progression been established, nor has the extent of alphaS pathology in the spinal cord been analyzed in population-based studies. Using immunohistochemistry, the frequency and distribution of alphaS pathology were assessed semiquantitatively in the brains and spinal cord nuclei of 304 subjects who were aged at least 85 in the population-based Vantaa 85+ study. alphaS pathology was common in the spinal cord; 102 (34%) subjects had classic alphaS pathology in the thoracic and/or sacral autonomic nuclei. Moreover, 134 (44%) subjects showed grain- or dot-like immunoreactivity in neuropil (mini-aggregates) without classic Lewy neurites or Lewy bodies (LBs). The latter type of alphaS accumulation is associated with age, but also the classic alphaS pathology was found more often in the oldest compared to the youngest age group. The severity of alphaS pathology in the spinal cord autonomic nuclei is significantly associated with the extent and severity of alphaS pathology in the brain. Of the subjects, 60% with moderate to severe thoracic alphaS pathology and up to 89% with moderate to severe sacral alphaS pathology had diffuse neocortical type of LB pathology in the brain. alphaS pathology exclusively in the spinal cord was rare. Our study indicates that in general alphaS pathology in the spinal cord autonomic nuclei is associated with similar pathology in the brain.
PubMed ID
20037761 View in PubMed
Less detail

APOE and AßPP gene variation in cortical and cerebrovascular amyloid-ß pathology and Alzheimer's disease: a population-based analysis.

https://arctichealth.org/en/permalink/ahliterature133862
Source
J Alzheimers Dis. 2011;26(2):377-85
Publication Type
Article
Date
2011
Author
Terhi Peuralinna
Maarit Tanskanen
Mira Mäkelä
Tuomo Polvikoski
Anders Paetau
Hannu Kalimo
Raimo Sulkava
John Hardy
Shiao-Lin Lai
Sampath Arepalli
Dena Hernandez
Bryan J Traynor
Andrew Singleton
Pentti J Tienari
Liisa Myllykangas
Author Affiliation
University of Helsinki, Research Program of Molecular Neurology, Biomedicum-Helsinki, Helsinki, Finland.
Source
J Alzheimers Dis. 2011;26(2):377-85
Date
2011
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Alleles
Alzheimer Disease - genetics - metabolism - pathology
Amyloid beta-Peptides - genetics - metabolism
Amyloid beta-Protein Precursor - genetics - metabolism
Apolipoproteins E - genetics - metabolism
Cerebral Amyloid Angiopathy - genetics - metabolism - pathology
Cerebral Cortex - metabolism - pathology
Female
Finland
Genetic Association Studies
Genetic Variation
Humans
Male
Middle Aged
Phenotype
Promoter Regions, Genetic
Abstract
Cortical and cerebrovascular amyloid-? (A?) deposition is a hallmark of Alzheimer's disease (AD), but also occurs in elderly people not affected by dementia. The apolipoprotein E (APOE) e4 is a major genetic modulator of A? deposition and AD risk. Variants of the amyloid-? protein precursor (A?PP) gene have been reported to contribute to AD and cerebral amyloid angiopathy (CAA). We analyzed the role of APOE and A?PP variants in cortical and cerebrovascular A? deposition, and neuropathologically verified AD (based on modified NIA-RI criteria) in a population-based autopsy sample of Finns aged = 85 years (Vantaa85 + Study; n = 282). Our updated analysis of APOE showed strong associations of the e4 allele with cortical (p = 4.91 ? 10-17) and cerebrovascular (p = 9.87 ? 10-11) A? deposition as well as with NIA-RI AD (p = 1.62 ? 10-8). We also analyzed 60 single nucleotide polymorphisms (SNPs) at the A?PP locus. In single SNP or haplotype analyses there were no statistically significant A?PP locus associations with cortical or cerebrovascular A? deposition or with NIA-RI AD. We sequenced the promoter of the A?PP gene in 40 subjects with very high A? deposition, but none of these subjects had any of the previously reported or novel AD-associated mutations. These results suggest that cortical and cerebrovascular A? depositions are useful quantitative traits for genetic studies, as highlighted by the strong associations with the APOE e4 variant. Promoter mutations or common allelic variation in the A?PP gene do not have a major contribution to cortical or cerebrovascular A? deposition, or very late-onset AD in this Finnish population based study.
Notes
Cites: Nat Genet. 2009 Oct;41(10):1088-9319734902
Cites: CNS Neurol Disord Drug Targets. 2009 Mar;8(1):16-3019275634
Cites: Curr Pharm Des. 2010;16(25):2766-7820698820
Cites: Neuropathol Appl Neurobiol. 2011 Apr;37(3):285-9420880354
Cites: Nat Genet. 2000 Jul;25(3):324-810888883
Cites: Acta Neuropathol. 2001 Jan;101(1):17-2111194935
Cites: Nat Rev Genet. 2000 Dec;1(3):182-9011252747
Cites: Neurology. 2001 Jun 26;56(12):1690-611425935
Cites: Nat Genet. 2001 Aug;28(4):309-1011479587
Cites: Am J Med Genet. 2002 Apr 8;114(3):288-9111920850
Cites: Nature. 2002 Apr 4;416(6880):535-911932745
Cites: Science. 2002 Jun 21;296(5576):2225-912029063
Cites: Science. 2002 Jul 19;297(5580):353-612130773
Cites: Arch Neurol. 2002 Nov;59(11):1793-912433268
Cites: Ann N Y Acad Sci. 2002 Nov;977:37-4412480732
Cites: Ann N Y Acad Sci. 2002 Nov;977:162-812480747
Cites: Brain. 1969 Mar;92(1):147-564237656
Cites: N Engl J Med. 1989 Jun 1;320(22):1446-522566117
Cites: Acta Neuropathol. 1990;79(5):569-721691573
Cites: Science. 1990 Jun 1;248(4959):1124-62111584
Cites: Nature. 1991 Feb 21;349(6311):704-61671712
Cites: Neurology. 1991 Apr;41(4):479-862011243
Cites: Am J Med Genet. 1991 Sep 15;40(4):449-531684090
Cites: Acta Neuropathol. 1991;82(4):239-591759558
Cites: Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-818446617
Cites: Science. 2009 Mar 13;323(5920):1473-719286555
Cites: Acta Neuropathol. 2009 Jul;118(1):115-3019225789
Cites: Acta Neuropathol. 2009 Oct;118(4):475-8519513731
Cites: N Engl J Med. 1995 Nov 9;333(19):1242-77566000
Cites: Ann N Y Acad Sci. 1997 Sep 26;826:263-719329698
Cites: Ann Neurol. 1998 Mar;43(3):380-39506555
Cites: Neurosci Lett. 1999 Jul 9;269(2):67-7010430506
Cites: Ann Neurol. 1999 Sep;46(3):382-9010482269
Cites: Bioinformatics. 2005 Jan 15;21(2):263-515297300
Cites: Neurobiol Aging. 2005 Nov-Dec;26(10):1329-4116243604
Cites: Neuropathol Appl Neurobiol. 2005 Dec;31(6):589-9916281907
Cites: Nat Genet. 2006 Jan;38(1):24-616369530
Cites: BMC Neurol. 2006;6:216401346
Cites: Am J Hum Genet. 2006 Jun;78(6):936-4616685645
Cites: Brain. 2006 Nov;129(Pt 11):2977-8316921174
Cites: Brain. 2006 Nov;129(Pt 11):2984-9116931535
Cites: Neurology. 2007 Feb 27;68(9):684-717325276
Cites: Am J Med Genet B Neuropsychiatr Genet. 2007 Jun 5;144B(4):469-7417427190
Cites: Am J Hum Genet. 2007 Sep;81(3):559-7517701901
Cites: Neurobiol Aging. 2008 Feb;29(2):194-20217112637
Cites: Ann Neurol. 2008 Sep;64(3):348-5218661559
Cites: Nat Genet. 2009 Oct;41(10):1094-919734903
PubMed ID
21654062 View in PubMed
Less detail

The Arctic Alzheimer mutation facilitates early intraneuronal Abeta aggregation and senile plaque formation in transgenic mice.

https://arctichealth.org/en/permalink/ahliterature6604
Source
Neurobiol Aging. 2006 Jan;27(1):67-77
Publication Type
Article
Date
Jan-2006
Author
Anna Lord
Hannu Kalimo
Chris Eckman
Xiao-Qun Zhang
Lars Lannfelt
Lars N G Nilsson
Author Affiliation
Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Dag Hammarskjölds Väg 20, SE-751 85 Uppsala, Sweden.
Source
Neurobiol Aging. 2006 Jan;27(1):67-77
Date
Jan-2006
Language
English
Publication Type
Article
Keywords
Aging - metabolism
Alzheimer Disease - genetics - metabolism
Amyloid beta-Protein - metabolism
Animals
Brain - metabolism
Disease Models, Animal
Genetic Predisposition to Disease - genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutagenesis, Site-Directed
Mutation
Neurons - metabolism
Protein Binding
Research Support, Non-U.S. Gov't
Senile Plaques - metabolism
Abstract
The Arctic mutation (APP E693G) is unique, since it is located within the amyloid-beta (Abeta) sequence and leads to Alzheimer's disease (AD). Arctic Abeta peptides more easily form Abeta protofibrils in vitro, but little is known about the pathogenic mechanism of the Arctic mutation in vivo. Here, we analyzed APP transgenic mice with both the Swedish and Arctic mutations (tg-APPArcSwe) and transgenic mice with the Swedish mutation alone (tg-APPSwe). Intense intraneuronal Abeta-immunoreactive staining was present in young tg-APPArcSwe mice, but not in tg-APPSwe mice. Intracellular Abeta aggregates in tg-APPArcSwe were strongly stained by antibodies recognizing the N-terminus of Abeta, while those recognizing the C-terminus of Abeta stained weakly. The Abeta aggregates inside neurons increased with age and predated extracellular Abeta deposition in both tg-APPArcSwe and tg-APPSwe mice. Senile plaque deposition was markedly accelerated in tg-APPArcSwe mice, as compared to tg-APPSwe mice. We conclude that the Arctic mutation causes AD by facilitating amyloidosis through early accumulation of intracellular Abeta aggregates in association with a rapid onset of senile plaque deposition.
PubMed ID
16298242 View in PubMed
Less detail

The Arctic amyloid-ß precursor protein (AßPP) mutation results in distinct plaques and accumulation of N- and C-truncated Aß.

https://arctichealth.org/en/permalink/ahliterature129327
Source
Neurobiol Aging. 2012 May;33(5):1010.e1-13
Publication Type
Article
Date
May-2012
Author
Ola Philipson
Anna Lord
Maciej Lalowski
Rabah Soliymani
Marc Baumann
Johan Thyberg
Nenad Bogdanovic
Tommie Olofsson
Lars O Tjernberg
Martin Ingelsson
Lars Lannfelt
Hannu Kalimo
Lars N G Nilsson
Author Affiliation
Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
Source
Neurobiol Aging. 2012 May;33(5):1010.e1-13
Date
May-2012
Language
English
Publication Type
Article
Keywords
Aged
Alzheimer Disease - genetics - metabolism - physiopathology
Amino Acid Substitution - genetics
Amyloid beta-Peptides - biosynthesis - chemistry - genetics
Amyloid beta-Protein Precursor - genetics - metabolism
Female
Humans
Male
Middle Aged
Molecular Weight
Peptide Fragments - biosynthesis - chemistry - genetics
Plaque, Amyloid - genetics - metabolism - pathology
Protein Isoforms - genetics - metabolism
Protein Structure, Tertiary - genetics
Abstract
The Arctic (p. E693G) mutation in the amyloid-ß precursor protein (AßPP) facilitates amyloid-ß (Aß) protofibril formation and generates clinical symptoms of Alzheimer's disease (AD). Here, molecular details of Aß in post mortem brain were investigated with biochemical and morphological techniques. The basic structure of Arctic plaques resembled cotton wool plaques. However, they appeared ring-formed with Aß42-specific antibodies, but were actually targetoid, since the periphery and center of many parenchymal Aß deposits stained differently with mid-domain, N- and C-terminal Aß antibodies. Aß fibrils were similar in shape, albeit shorter than in sporadic AD brain, when examined by electron microscopy. Aßwild-type and Aßarctic codeposited and parenchymal deposits were highly enriched in both N- and C-terminally truncated Aß. In contrast, cerebral amyloid angiopathy (CAA) contained a substantial amount of Aß1-40. The absence of plaques with cores of fibrillary Aß might be due to the scarcity of full-length Aß, although other mechanisms could be involved. Our findings are discussed in relation to mechanisms and relevance of amyloid formation and to the clinical features of AD.
PubMed ID
22118948 View in PubMed
Less detail

Bedside diagnosis of rippling muscle disease in CAV3 p.A46T mutation carriers.

https://arctichealth.org/en/permalink/ahliterature97708
Source
Muscle Nerve. 2010 Jun;41(6):751-7
Publication Type
Article
Date
Jun-2010
Author
Jimmy Sundblom
Erik Stålberg
Maria Osterdahl
Franz Rücker
Maria Montelius
Hannu Kalimo
Inger Nennesmo
Gunilla Islander
Anja Smits
Niklas Dahl
Atle Melberg
Author Affiliation
Department of Neuroscience, Neurology, University Hospital, Uppsala University SE-751 85 Uppsala, Sweden. jimmy.sundblom@neuro.uu.se
Source
Muscle Nerve. 2010 Jun;41(6):751-7
Date
Jun-2010
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Caveolin 3 - genetics
Child
Child, Preschool
Electromyography
Female
Humans
Male
Middle Aged
Muscular Diseases - genetics - physiopathology
Neurophysiology
Pedigree
Point-of-Care Systems
Polymorphism, Single Nucleotide
Sweden
Abstract
Thirty-nine members, ages 1 to 67 years, of a Swedish family with rippling muscle disease (RMD) were investigated to assess genotype-phenotype correlations. Clinical, neurophysiological, and muscle morphological examinations were performed. Genetic analysis was performed in 38 individuals. Twenty-three patients had percussion-induced muscle mounding (PIMM) and percussion-induced rapid contractions (PIRC). Rippling and hyperCKemia were not found in all patients. Weakness was minor or absent. The electromyogram showed absence of electrical activity in ripples and PIMM, and muscle biopsy specimens confirmed caveolin-3 deficiency and absence of caveolae. Genetic analysis revealed a CAV3 c.G136A transition resulting in a p.A46T missense mutation in affected family members. The phenotype in these 23 cases of RMD with this mutation appears to be homogenous, benign, and nonprogressive. The presence of PIMM and PIRC seems to be diagnostic at all ages, whereas the absence of hyperCKemia and rippling does not exclude the diagnosis.
PubMed ID
20229577 View in PubMed
Less detail

Four new Finnish families with LGMD1D; refinement of the clinical phenotype and the linked 7q36 locus.

https://arctichealth.org/en/permalink/ahliterature136456
Source
Neuromuscul Disord. 2011 May;21(5):338-44
Publication Type
Article
Date
May-2011
Author
Peter Hackman
Satu Sandell
Jaakko Sarparanta
Helena Luque
Sanna Huovinen
Johanna Palmio
Anders Paetau
Hannu Kalimo
Ibrahim Mahjneh
Bjarne Udd
Author Affiliation
Folkhälsan Institute of Genetics and Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland. peter.hackman@helsinki.fi
Source
Neuromuscul Disord. 2011 May;21(5):338-44
Date
May-2011
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Child
Child, Preschool
Chromosome Mapping
Chromosomes, Human, Pair 7 - genetics
Creatine Kinase - blood
Electrocardiography
Electromyography
Family Health
Female
Finland - ethnology
Genetic Linkage
Genotype
Humans
Male
Molecular Biology - methods
Muscular Dystrophies, Limb-Girdle - genetics - pathology
Phenotype
Young Adult
Abstract
The objective is to refine the clinical and morphological phenotype and the chromosomal region of interest, in the recently reported 7q36 linked autosomal dominant limb-girdle muscular dystrophy (LGMD1 D/E), by describing four new informative Finnish families. Examinations of the patients included serum CK, neurophysiological studies, cardiac and respiratory function examinations, muscle biopsies and muscle imaging. DNA samples were analyzed by genotyping. Patients in all families had very similar phenotypes with onset of muscle weakness in the pelvic girdle muscles between the fourth and sixth decade, later involvement of the shoulder girdle, and marked walking difficulties in the eighth decade. Muscle biopsies showed myopathic and/or dystrophic features. Genotyping confirmed linkage to the same locus at chromosome 7q36 in all families by one identically segregating haplotype. The linked region was narrowed down from
PubMed ID
21376592 View in PubMed
Less detail

A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD.

https://arctichealth.org/en/permalink/ahliterature131029
Source
Neuron. 2011 Oct 20;72(2):257-68
Publication Type
Article
Date
Oct-20-2011
Author
Alan E Renton
Elisa Majounie
Adrian Waite
Javier Simón-Sánchez
Sara Rollinson
J Raphael Gibbs
Jennifer C Schymick
Hannu Laaksovirta
John C van Swieten
Liisa Myllykangas
Hannu Kalimo
Anders Paetau
Yevgeniya Abramzon
Anne M Remes
Alice Kaganovich
Sonja W Scholz
Jamie Duckworth
Jinhui Ding
Daniel W Harmer
Dena G Hernandez
Janel O Johnson
Kin Mok
Mina Ryten
Danyah Trabzuni
Rita J Guerreiro
Richard W Orrell
James Neal
Alex Murray
Justin Pearson
Iris E Jansen
David Sondervan
Harro Seelaar
Derek Blake
Kate Young
Nicola Halliwell
Janis Bennion Callister
Greg Toulson
Anna Richardson
Alex Gerhard
Julie Snowden
David Mann
David Neary
Michael A Nalls
Terhi Peuralinna
Lilja Jansson
Veli-Matti Isoviita
Anna-Lotta Kaivorinne
Maarit Hölttä-Vuori
Elina Ikonen
Raimo Sulkava
Michael Benatar
Joanne Wuu
Adriano Chiò
Gabriella Restagno
Giuseppe Borghero
Mario Sabatelli
David Heckerman
Ekaterina Rogaeva
Lorne Zinman
Jeffrey D Rothstein
Michael Sendtner
Carsten Drepper
Evan E Eichler
Can Alkan
Ziedulla Abdullaev
Svetlana D Pack
Amalia Dutra
Evgenia Pak
John Hardy
Andrew Singleton
Nigel M Williams
Peter Heutink
Stuart Pickering-Brown
Huw R Morris
Pentti J Tienari
Bryan J Traynor
Author Affiliation
Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Source
Neuron. 2011 Oct 20;72(2):257-68
Date
Oct-20-2011
Language
English
Publication Type
Article
Keywords
Alleles
Amyotrophic Lateral Sclerosis - genetics
Chromosomes, Human, Pair 9
Female
Finland
Frontotemporal Dementia - genetics
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Male
Microsatellite Repeats
Pedigree
Polymorphism, Single Nucleotide
Abstract
The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype, covering the MOBKL2b, IFNK, and C9ORF72 genes, is present in the majority of cases linked to this region. Here we show that there is a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the affected haplotype. This repeat expansion segregates perfectly with disease in the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic ALS in that population. Taken together with the D90A SOD1 mutation, 87% of familial ALS in Finland is now explained by a simple monogenic cause. The repeat expansion is also present in one-third of familial ALS cases of outbred European descent, making it the most common genetic cause of these fatal neurodegenerative diseases identified to date.
Notes
Cites: J Clin Neurosci. 2009 Sep;16(9):1131-519556136
Cites: Bioinformatics. 2009 Jul 15;25(14):1754-6019451168
Cites: Nat Genet. 2010 Mar;42(3):234-920154673
Cites: Nature. 2010 May 13;465(7295):223-620428114
Cites: Hum Mol Genet. 2010 Apr 15;19(R1):R46-6420400460
Cites: Genome Res. 2010 Sep;20(9):1297-30320644199
Cites: Lancet Neurol. 2010 Oct;9(10):986-9420801717
Cites: Lancet Neurol. 2010 Oct;9(10):978-8520801718
Cites: Lancet Neurol. 2010 Oct;9(10):995-100720864052
Cites: Neuron. 2010 Dec 9;68(5):857-6421145000
Cites: J Neurol Neurosurg Psychiatry. 2011 Feb;82(2):196-20320562461
Cites: J Neurol. 2011 Apr;258(4):647-5521072532
Cites: Am J Hum Genet. 2011 Jul 15;89(1):121-3021683323
Cites: Hum Mol Genet. 2011 Oct 1;20(19):3811-2121729883
Cites: J Neurochem. 2011 Oct;119(2):275-8221848658
Cites: Neuron. 2011 Oct 20;72(2):245-5621944778
Cites: Neurobiol Aging. 2012 Jan;33(1):209.e3-821925771
Cites: Neurology. 2006 Mar 28;66(6):839-4416421333
Cites: Nat Genet. 2009 Oct;41(10):1083-719734901
Cites: Science. 2009 Feb 27;323(5918):1208-1119251628
Cites: Science. 2009 Feb 27;323(5918):1205-819251627
Cites: Science. 2008 Mar 21;319(5870):1668-7218309045
Cites: N Engl J Med. 2001 May 31;344(22):1688-70011386269
Cites: Cell. 1999 Dec 23;99(7):703-1210619424
Cites: Science. 2002 Apr 12;296(5566):261-211954565
Cites: Nature. 1993 Mar 4;362(6415):59-628446170
Cites: Nat Genet. 1996 Feb;12(2):183-58563757
Cites: J Med Genet. 1996 Dec;33(12):1022-69004136
Cites: Brain. 2006 Apr;129(Pt 4):868-7616495328
Cites: Science. 2006 Oct 6;314(5796):130-317023659
Cites: Neurology. 2007 Jan 30;68(5):326-3717261678
Cites: Am J Hum Genet. 2007 Sep;81(3):559-7517701901
Cites: Neurology. 2008 Feb 12;70(7):533-718268245
Comment In: Clin Genet. 2012 Feb;81(2):126-722129088
Comment In: Nat Rev Neurol. 2011 Nov;7(11):59522009283
Comment In: Mov Disord. 2012 Feb;27(2):20222423382
Comment In: Neuron. 2011 Oct 20;72(2):189-9022017980
PubMed ID
21944779 View in PubMed
Less detail

A highly insoluble state of Abeta similar to that of Alzheimer's disease brain is found in Arctic APP transgenic mice.

https://arctichealth.org/en/permalink/ahliterature159372
Source
Neurobiol Aging. 2009 Sep;30(9):1393-405
Publication Type
Article
Date
Sep-2009
Author
Ola Philipson
Per Hammarström
K Peter R Nilsson
Erik Portelius
Tommie Olofsson
Martin Ingelsson
Bradley T Hyman
Kaj Blennow
Lars Lannfelt
Hannu Kalimo
Lars N G Nilsson
Author Affiliation
Department of Public Health and Caring Science, Uppsala University, Sweden.
Source
Neurobiol Aging. 2009 Sep;30(9):1393-405
Date
Sep-2009
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Alzheimer Disease - genetics - metabolism - physiopathology
Amyloid beta-Peptides - antagonists & inhibitors - chemistry - metabolism
Amyloid beta-Protein Precursor - genetics
Animals
Antibodies - pharmacology - therapeutic use
Brain - metabolism - pathology - physiopathology
Disease Models, Animal
Genetic Predisposition to Disease - genetics
Humans
Mice
Mice, Transgenic
Microscopy, Electron, Transmission
Mutation - genetics
Plaque, Amyloid - genetics - metabolism - pathology
Solubility
Abstract
Amyloid-beta (Abeta) is a major drug target in Alzheimer's disease. Here, we demonstrate that deposited Abeta is SDS insoluble in tgAPP-ArcSwe, a transgenic mouse model harboring the Arctic (E693G) and Swedish (KM670/671NL) APP mutations. Formic acid was needed to extract the majority of deposited Abeta in both tgAPP-ArcSwe and Alzheimer's disease brain, but not in a commonly used type of mouse model with the Swedish mutation alone. Interestingly, the insoluble state of Arctic Abeta was determined early on and did not gradually evolve with time. In tgAPP-ArcSwe, Abeta plaques displayed a patchy morphology with bundles of Abeta fibrils, whereas amyloid cores in tgAPP-Swe were circular with radiating fibrils. Amyloid was more densely stacked in tgAPP-ArcSwe, as demonstrated with a conformation sensitive probe. A reduced increase in plasma Abeta was observed following acute administration of an Abeta antibody in tgAPP-ArcSwe, results that might imply reduced brain to plasma Abeta efflux. TgAPP-ArcSwe, with its insoluble state of deposited Abeta, could serve as a complementary model to better predict the outcome of clinical trials.
PubMed ID
18192084 View in PubMed
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Mitochondrial DNA sequence variation and mutation rate in patients with CADASIL.

https://arctichealth.org/en/permalink/ahliterature168576
Source
Neurogenetics. 2006 Jul;7(3):185-94
Publication Type
Article
Date
Jul-2006
Author
Johanna Annunen-Rasila
Saara Finnilä
Kati Mykkänen
Jukka S Moilanen
Johanna Veijola
Minna Pöyhönen
Matti Viitanen
Hannu Kalimo
Kari Majamaa
Author Affiliation
Department of Neurology, University of Oulu, Oulu, Finland.
Source
Neurogenetics. 2006 Jul;7(3):185-94
Date
Jul-2006
Language
English
Publication Type
Article
Keywords
Adult
Aged, 80 and over
CADASIL - genetics
Case-Control Studies
DNA, Mitochondrial - genetics
Female
Finland
Genetic Predisposition to Disease
Genetic Variation
Haplotypes
Humans
Male
Middle Aged
Mutation
Open Reading Frames
Pedigree
Polymorphism, Genetic
Receptors, Notch - genetics
Abstract
Mutations in the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is clinically characterised by recurrent ischemic strokes, migraine with aura, psychiatric symptoms, cognitive decline and dementia. We have previously described a patient with CADASIL caused by a R133C mutation in the NOTCH3 gene and with a concomitant myopathy caused by a 5650G>A mutation in the MTTA gene in mitochondrial DNA (mtDNA). We assume that the co-occurrence of the two mutations is not coincidental and that mutations in the NOTCH3 gene may predispose the mtDNA to mutations. We therefore examined the nucleotide variation in the mtDNA coding region sequences in 20 CADASIL pedigrees with 77 affected patients by conformation-sensitive gel electrophoresis and sequencing. The sequence variation in mtDNA was then compared with that among 192 healthy Finns. A total of 180 mtDNA coding region sequence differences were found relative to the revised Cambridge reference sequence, including five novel synonymous substitutions, two novel nonsynonymous substitutions and one novel tRNA substitution. We found that maternal relatives in two pedigrees differed from each other in their mtDNA. Furthermore, the average number of pairwise differences in sequences from the 41 unrelated maternal lineages with CADASIL was higher than that expected among haplogroup-matched controls. The numbers of polymorphic sites and polymorphisms that were present in only one sequence were also higher among the CADASIL sequences than among the control sequences. Our results show that mtDNA sequence variation is increased within CADASIL pedigrees. These findings suggest a relationship between NOTCH3 and mtDNA.
Notes
Erratum In: Neurogenetics. 2006 Nov;7(4):281
PubMed ID
16807713 View in PubMed
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