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• Heterogeneous age-related breakdown of white matter structural integrity: implications for cortical "disconnection" in aging and Alzheimer's disease.
• Citation:
  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
  [PubMed] [Alzforum]
• Supporting:
  • Myelin and its components such as cholesterol and myelin proteins are reduced in old age and are substantially further reduced in mild cognitive impairment (MCI) and AD.

    SHOW Details   Supporting(6)   Consistent(2)   Alternative to: (2)

    Experimental Approach: Mechanism - molecular and cell,  
    Pathogenic Narrative Tags: Pathogenic event
    Supporting Evidence
    

    • Gottfries C, Karlsson I, Svennerholm L
      Membrane components separate early-onset Alzheimer's disease from senile dementia of the Alzheimer type.
      International psychogeriatrics / IPA. 1996;8(3):365-72
    • Sjöbeck M, Haglund M, Englund E
      Decreasing myelin density reflected increasing white matter pathology in Alzheimer's disease--a neuropathological study.
      International journal of geriatric psychiatry. 2005 Oct;20(10):919-26
    • 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
    • Han X, M Holtzman D, McKeel D, Kelley J, Morris J
      Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis.
      Journal of neurochemistry. 2002 Aug;82(4):809-18
    • House M, St Pierre T, Foster J, Martins R, Clarnette R
      Quantitative MR imaging R2 relaxometry in elderly participants reporting memory loss.
      AJNR. American journal of neuroradiology. 2006 Feb;27(2):430-9
    • Roher A, Weiss N, Kokjohn T, Kuo Y, Kalback W, Anthony J, Watson D, Luehrs D, Sue L, Walker D, Emmerling M, Goux W, Beach T
      Increased A beta peptides and reduced cholesterol and myelin proteins characterize white matter degeneration in Alzheimer's disease.
      Biochemistry. 2002 Sep 17;41(37):11080-90

    Consistent statements
    

    • The decrease of membrane cholesterol provokes a release of Aβ peptides from the membranes, so that they accumulate in the extracellular space where they are not toxic. Russo T 
    • Cholesterol is implicated with AD pathogenesis.

    Alternative statements
    

    • High cholesterol diets increase Aβ pathology in animals. Hardy J  Selkoe D 
    • Cholesterol lowering drugs reduce pathology in APP transgenic mice. Hardy J  Selkoe D 
  • 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.

    SHOW Details   Supporting(18) 

    Experimental Approach:
    Pathogenic Narrative Tags:
    Supporting Evidence
    

    • 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
    • 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
      BRAIN MYELINATION IN PREVALENT NEUROPSYCHIATRIC DEVELOPMENTAL DISORDERS: PRIMARY AND COMORBID ADDICTION.
      Adolescent psychiatry. 2005;29:55-96
    • 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
    • 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.
      Brain : a journal of neurology. 2007 Oct;130(Pt 10):2508-19
    • 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
    • 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
    • Bartzokis G, Lu P, Tishler T, Fong S, Oluwadara B, Finn J, Huang D, Bordelon Y, 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
    • 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, 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
• Created On: Mon, Mar 01 18:07:22 EST 2010
• Last Modified On: Mon Mar 01 18:07:22 EST 2010