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Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals: implications for cognitive decline and dementia.
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Reduced fast axonal transport with resultant axonal swellings suggests white matter and myelin involvement in AD and many disorders including Huntington’s disease, amyotrophic lateral sclerosis, schizophrenia, insult-based disorders such as TBI and toxic substance exposure, as well as myelin-based inflammatory disorders such as multiple sclerosis; this diversity of diseases confirms a hypothesis of a “weakest link”/“highest repair priority” status for vertebrate myelin especially in human CNS.
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Supporting(18)
Experimental Approach:
Pathogenic Narrative Tags:
Supporting Evidence
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Pfefferbaum A,
Adalsteinsson E,
Sullivan E
Supratentorial profile of white matter microstructural integrity in recovering alcoholic men and women.
Biological psychiatry. 2006 Feb 15;59(4):364-72 -
Abe K,
Fujimura H,
Kobayashi Y,
Fujita N,
Yanagihara T
Degeneration of the pyramidal tracts in patients with amyotrophic lateral sclerosis. A premortem and postmortem magnetic resonance imaging study.
Journal of neuroimaging : official journal of the American Society of Neuroimaging. 1997 Oct;7(4):208-12 -
Bartzokis G,
Lu P,
Tishler T,
Fong S,
Oluwadara B,
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Mintz J,
Perlman S
Myelin breakdown and iron changes in Huntington's disease: pathogenesis and treatment implications.
Neurochemical research. 2007 Oct;32(10):1655-64 -
Bartzokis G
Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease.
Neurobiology of aging. 2004 Jan;25(1):5-18; author reply 49-62 -
Ringman J,
O'Neill J,
Geschwind D,
Medina L,
Apostolova L,
Rodriguez Y,
Schaffer B,
Varpetian A,
Tseng B,
Ortiz F,
Fitten J,
Cummings J,
Bartzokis G
Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations.
Brain : a journal of neurology. 2007 Jul;130(Pt 7):1767-76 -
Wirths O,
Weis J,
Kayed R,
Saido T,
Bayer T
Age-dependent axonal degeneration in an Alzheimer mouse model.
Neurobiology of aging. 2007 Nov;28(11):1689-99 -
Bartzokis G,
Beckson M,
Lu P,
Nuechterlein K,
Edwards N,
Mintz J
Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study.
Archives of general psychiatry. 2001 May;58(5):461-5 -
Bartzokis G,
Sultzer D,
Lu P,
Nuechterlein K,
Mintz J,
Cummings J
Heterogeneous age-related breakdown of white matter structural integrity: implications for cortical "disconnection" in aging and Alzheimer's disease.
Neurobiology of aging. 2004 Aug;25(7):843-51 -
Mori H,
Yagishita A,
Takeda T,
Mizutani T
Symmetric temporal abnormalities on MR imaging in amyotrophic lateral sclerosis with dementia.
AJNR. American journal of neuroradiology. 2007 Sep;28(8):1511-6 -
Aboul-Enein F,
Weiser P,
Höftberger R,
Lassmann H,
Bradl M
Transient axonal injury in the absence of demyelination: a correlate of clinical disease in acute experimental autoimmune encephalomyelitis.
Acta neuropathologica. 2006 Jun;111(6):539-47 -
Liu M,
Akle V,
Zheng W,
Kitlen J,
O'Steen B,
Larner S,
Dave J,
Tortella F,
Hayes R,
Wang K
Extensive degradation of myelin basic protein isoforms by calpain following traumatic brain injury.
Journal of neurochemistry. 2006 Aug;98(3):700-12 -
Kraus M,
Susmaras T,
Caughlin B,
Walker C,
Sweeney J,
Little D
White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study.
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Adalbert R,
Gilley J,
Coleman M
Abeta, tau and ApoE4 in Alzheimer's disease: the axonal connection.
Trends in molecular medicine. 2007 Apr;13(4):135-42 -
Bartzokis G
BRAIN MYELINATION IN PREVALENT NEUROPSYCHIATRIC DEVELOPMENTAL DISORDERS: PRIMARY AND COMORBID ADDICTION.
Adolescent psychiatry. 2005;29:55-96 -
Bartzokis G
Schizophrenia: breakdown in the well-regulated lifelong process of brain development and maturation.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2002 Oct;27(4):672-83 -
Fennema-Notestine C,
Archibald S,
Jacobson M,
Corey-Bloom J,
Paulsen J,
Peavy G,
Gamst A,
Hamilton J,
Salmon D,
Jernigan T
In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease.
Neurology. 2004 Sep 28;63(6):989-95 -
Bartzokis G,
Lu P,
Geschwind D,
Edwards N,
Mintz J,
Cummings J
Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals: implications for cognitive decline and dementia.
Archives of general psychiatry. 2006 Jan;63(1):63-72 -
Haroutunian V,
Davis K
Introduction to the special section: Myelin and oligodendrocyte abnormalities in schizophrenia.
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 2007 Aug;10(4):499-502
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Impaired myelin repair may mediate the increased age-related decline of myelin integrity and cognitive performance of healthy ApoE4+ carriers resulting in increased rates of AD.
SHOW Details Supporting(5)
Genes/Proteins: (1)
Experimental Approach:
Pathogenic Narrative Tags:
Supporting Evidence
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Bartzokis G,
Lu P,
Tingus K,
Mendez M,
Richard A,
Peters D,
Oluwadara B,
Barrall K,
Finn J,
Villablanca P,
Thompson P,
Mintz J
Lifespan trajectory of myelin integrity and maximum motor speed.
Neurobiology of aging. 2008 Oct 15; -
Bartzokis G,
Beckson M,
Lu P,
Nuechterlein K,
Edwards N,
Mintz J
Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study.
Archives of general psychiatry. 2001 May;58(5):461-5 -
Bartzokis G,
Cummings J,
Sultzer D,
Henderson V,
Nuechterlein K,
Mintz J
White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study.
Archives of neurology. 2003 Mar;60(3):393-8 -
Bartzokis G,
Lu P,
Geschwind D,
Edwards N,
Mintz J,
Cummings J
Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals: implications for cognitive decline and dementia.
Archives of general psychiatry. 2006 Jan;63(1):63-72 -
Bartzokis G,
Lu P,
Geschwind D,
Tingus K,
Huang D,
Mendez M,
Edwards N,
Mintz J
Apolipoprotein E affects both myelin breakdown and cognition: implications for age-related trajectories of decline into dementia.
Biological psychiatry. 2007 Dec 15;62(12):1380-7
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The myelin model proposes that ApoE4+ individuals are poor in recycling lipid debris for reuse in myelin repair whereas this is enhanced in ApoE2+ individuals, including the removal of myelin sulfatide debris which is also ApoE-dependent and critically important for successful repair.
SHOW Details Supporting(4)
Genes/Proteins: (1)
Experimental Approach:
Pathogenic Narrative Tags:
Supporting Evidence
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Halder R,
Jahng A,
Maricic I,
Kumar V
Mini review: immune response to myelin-derived sulfatide and CNS-demyelination.
Neurochemical research. 2007 Feb;32(2):257-62 -
Bartzokis G,
Lu P,
Geschwind D,
Edwards N,
Mintz J,
Cummings J
Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals: implications for cognitive decline and dementia.
Archives of general psychiatry. 2006 Jan;63(1):63-72 -
Cheng H,
Zhou Y,
Holtzman D,
Han X
Apolipoprotein E mediates sulfatide depletion in animal models of Alzheimer's disease.
Neurobiology of aging. 2008 Aug 30; -
Kanter J,
Narayana S,
Ho P,
Catz I,
Warren K,
Sobel R,
Steinman L,
Robinson W
Lipid microarrays identify key mediators of autoimmune brain inflammation.
Nature medicine. 2006 Jan;12(1):138-43
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Neuregulin signaling and BACE1 activation may be important in repair of later- more thinly myelinated regions where age-related myelin breakdown is most pronounced.
SHOW Details Supporting(4)
Alternative to: (1)
Genes/Proteins: (2)
Description: The myelination of smaller and more thinly-myelinated fibers seems disproportionately dependent on neuregulin signaling compared to larger and more thickly-myelinated fibers.Genes/Proteins
Experimental Approach: Mechanism - biochemistry and structural biology, Mechanism - molecular and cell
Pathogenic Narrative Tags:
Supporting Evidence
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Taveggia C,
Thaker P,
Petrylak A,
Caporaso G,
Toews A,
Falls D,
Einheber S,
Salzer J
Type III neuregulin-1 promotes oligodendrocyte myelination.
Glia. 2008 Feb;56(3):284-93 -
Bartzokis G,
Lu P,
Geschwind D,
Edwards N,
Mintz J,
Cummings J
Apolipoprotein E genotype and age-related myelin breakdown in healthy individuals: implications for cognitive decline and dementia.
Archives of general psychiatry. 2006 Jan;63(1):63-72 -
Michailov G,
Sereda M,
Brinkmann B,
Fischer T,
Haug B,
Birchmeier C,
Role L,
Lai C,
Schwab M,
Nave K
Axonal neuregulin-1 regulates myelin sheath thickness.
Science (New York, N.Y.). 2004 Apr 30;304(5671):700-3 -
Bartzokis G,
Lu P,
Geschwind D,
Tingus K,
Huang D,
Mendez M,
Edwards N,
Mintz J
Apolipoprotein E affects both myelin breakdown and cognition: implications for age-related trajectories of decline into dementia.
Biological psychiatry. 2007 Dec 15;62(12):1380-7
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PubMed
