title: Increased A beta peptides and reduced cholesterol and myelin proteins characterize white matter degeneration in Alzheimer's disease.
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 Abeta40 and Abeta42 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.
authors.affiliation: The Longtine Center for Molecular Biology and Genetics and Harold Civin Laboratory of Neuropathology, Sun Health Research Institute, Sun City, Arizona 85351, USA. alex.roher@sunbreath.org
authors.forename: Alex E
authors.initials: AE
authors.lastname: Roher
authors.forename: Nicole
authors.initials: N
authors.lastname: Weiss
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Kokjohn
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Kuo
authors.forename: Walter
authors.initials: W
authors.lastname: Kalback
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Anthony
authors.forename: Desiree
authors.initials: D
authors.lastname: Watson
authors.forename: Dean C
authors.initials: DC
authors.lastname: Luehrs
authors.forename: Lucia
authors.initials: L
authors.lastname: Sue
authors.forename: Douglas
authors.initials: D
authors.lastname: Walker
authors.forename: Mark
authors.initials: M
authors.lastname: Emmerling
authors.forename: Warren
authors.initials: W
authors.lastname: Goux
authors.forename: Thomas
authors.initials: T
authors.lastname: Beach
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism*; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005227:Fatty Acids; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D002784:Cholesterol; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571337:CNP protein, human