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

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, and Paul L. Wood

Phenomenome Discoveries Inc., Saskatoon, SK S7N 4L8

Corresponding Author: d.goodenowe{at}phenomenome.com

Although Dementia of the Alzheimer’s type (DAT) is the most common form of dementia, dementia severity is only weakly correlated with DAT pathology. In contrast, post-mortem measurements of cholinergic function and membrane ethanolamine plasmalogen (PlsEtn) content in the cortex and hippocampus each correlate with the severity of dementia in DAT. Currently, the largest risk factor for DAT is age. Since the synthesis of PlsEtn occurs via a single non-redundant peroxisomal pathway that has been shown to decrease with age and PlsEtn are 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 over 400 clinically demented and over 350 non-demented 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. Further, a linear regression model predicted that serum PlsEtn decrease years prior to clinical symptoms. The putative roles that ethanolamine plasmalogen biochemistry play in the etiology of cholinergic degeneration, amyloid accumulation and dementia are discussed.

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