Relative to the
gray matter, there is a paucity of information re
gardin
g white matter biochemicalalterations and their contribution to Alzheimer's disease (AD). Biochemical analyses of AD white mattercombinin
g size-exclusion, normal phase, and
gas chromato
graphy, immunoassays, and Western blottin
grevealed increased quantities of A
ges/
gifchars/beta2.
gif" BORDER=0 ALIGN="middle">40 and A
ges/
gifchars/beta2.
gif" BORDER=0 ALIGN="middle">42 in AD white matter accompanied by si
gnificant 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 si
gnificantly decreasedwhile total fatty acid content was increased. In some instances, these white matter biochemical alterationswere correlated with patient apolipoprotein E
genotype, Braak sta
ge, and
gender. Our observations su
ggestthat extensive white matter axonal demyelination underlies Alzheimer's patholo
gy, resultin
g in loss ofcapacitance and serious disturbances in nerve conduction, severely dama
gin
g brain function. These whitematter alterations undoubtedly contribute to AD patho
genesis and may represent the combined effects ofneuronal de
generation, micro
gliosis, oli
godendrocyte 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 patholo
gy.