Peripheral ethanolamine plasmalogen deficiency: a logical causative factor in Alzheimer's disease and dementia

Autor: Dayan B. Goodenowe, Lisa L. Cook, Jun Liu, Yingshen Lu, Dushmanthi A. Jayasinghe, Pearson W.K. Ahiahonu, Doug Heath, Yasuyo Yamazaki, John Flax, Kevin F. Krenitsky, D.L. Sparks, Alan Lerner, Robert P. Friedland, Takashi Kudo, Kouzin Kamino, Takashi Morihara, Masatoshi Takeda, Paul L. Wood
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Zdroj: Journal of Lipid Research, Vol 48, Iss 11, Pp 2485-2498 (2007)
Druh dokumentu: article
ISSN: 0022-2275
DOI: 10.1194/jlr.P700023-JLR200
Popis: Although dementia of the Alzheimer's type (DAT) is the most common form of dementia, the severity of dementia is only weakly correlated with DAT pathology. In contrast, postmortem measurements of cholinergic function and membrane ethanolamine plasmalogen (PlsEtn) content in the cortex and hippocampus correlate with the severity of dementia in DAT. Currently, the largest risk factor for DAT is age. Because the synthesis of PlsEtn occurs via a single nonredundant peroxisomal pathway that has been shown to decrease with age and PlsEtn is decreased in the DAT brain, we investigated potential relationships between serum PlsEtn levels, dementia severity, and DAT pathology. In total, serum PlsEtn levels were measured in five independent population collections comprising >400 clinically demented and >350 nondemented subjects. Circulating PlsEtn levels were observed to be significantly decreased in serum from clinically and pathologically diagnosed DAT subjects at all stages of dementia, and the severity of this decrease correlated with the severity of dementia. Furthermore, a linear regression model predicted that serum PlsEtn levels decrease years before clinical symptoms. The putative roles that PlsEtn biochemistry play in the etiology of cholinergic degeneration, amyloid accumulation, and dementia are discussed.
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