Relative to the gray
matter, there is a paucity of information regarding
white matter biochemicalalterations and their contribution to Alzheimer's disease (AD). Biochemical analyses of AD
white mattercombining size-exclusion, normal phase, and gas chromatography, immunoassays, and Western blottingrevealed increased quantities of A
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40 and A
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42 in AD
white matter accompanied by significant decreasesin the amounts of myelin basic protein, myelin proteolipid protein, and 2',3'-cyclic nucleotide3'-phosphodiesterase. In addition, the AD
white matter cholesterol levels were significantly decreasedwhile total fatty acid content was increased. In some instances, these
white matter biochemical alterationswere correlated with patient apolipoprotein E genotype, Braak stage, and gender. Our observations suggestthat extensive
white matter axonal demyelination underlies Alzheimer's pathology, resulting in loss ofcapacitance and serious disturbances in nerve conduction, severely damaging brain function. These
whitematter alterations undoubtedly contribute to AD pathogenesis and may represent the combined effects ofneuronal degeneration, microgliosis, oligodendrocyte
injury, microcirculatory disease, and interstitial fluidstasis. To accurately assess the success of future therapeutic interventions, it is necessary to have a completeappreciation of the full scope and extent of AD pathology.