Increased Aβ peptides and reduced cholesterol and myelin proteins characterize white matter degeneration in Alzheimer's disease

Alex E. Roher, Nicole Weiss, Tyler A. Kokjohn, Yu Min Kuo, Walter Kalback, Jacqueline Anthony, Desiree Watson, Dean C. Luehrs, Lucia Sue, Douglas Walker, Mark Emmerling, Warren Goux, Thomas Beach

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196 Citations (Scopus)

Abstract

Relative to the gray matter, there is a paucity of information regarding white matter biochemical alterations and their contribution to Alzheimer's disease (AD). Biochemical analyses of AD white matter combining size-exclusion, normal phase, and gas chromatography, immunoassays, and Western blotting revealed increased quantities of Aβ40 and Aβ42 in AD white matter accompanied by significant decreases in the amounts of myelin basic protein, myelin proteolipid protein, and 2′,3′-cyclic nucleotide 3′-phosphodiesterase. In addition, the AD white matter cholesterol levels were significantly decreased while total fatty acid content was increased. In some instances, these white matter biochemical alterations were correlated with patient apolipoprotein E genotype, Braak stage, and gender. Our observations suggest that extensive white matter axonal demyelination underlies Alzheimer's pathology, resulting in loss of capacitance and serious disturbances in nerve conduction, severely damaging brain function. These white matter alterations undoubtedly contribute to AD pathogenesis and may represent the combined effects of neuronal degeneration, microgliosis, oligodendrocyte injury, microcirculatory disease, and interstitial fluid stasis. To accurately assess the success of future therapeutic interventions, it is necessary to have a complete appreciation of the full scope and extent of AD pathology.

Original languageEnglish
Pages (from-to)11080-11090
Number of pages11
JournalBiochemistry
Volume41
Issue number37
DOIs
Publication statusPublished - 2002 Sep 17

All Science Journal Classification (ASJC) codes

  • Biochemistry

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    Roher, A. E., Weiss, N., Kokjohn, T. A., Kuo, Y. M., Kalback, W., Anthony, J., Watson, D., Luehrs, D. C., Sue, L., Walker, D., Emmerling, M., Goux, W., & Beach, T. (2002). Increased Aβ peptides and reduced cholesterol and myelin proteins characterize white matter degeneration in Alzheimer's disease. Biochemistry, 41(37), 11080-11090. https://doi.org/10.1021/bi026173d