Circulating plasmalogen levels and Alzheimer Disease Assessment Scale–Cognitive scores in Alzheimer patients

Abstract

59Background: Plasmalogens, which are key structural phospholipids in brain membranes, are decreased in the brain and serum of patients with Alzheimer disease (AD). We performed this pilot study to evaluate the relation between the levels of circulating plasmalogens and Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) scores in patients with AD. Methods: We evaluated participants' ADAS-Cog scores and serum plasmalogen levels. For the 40 included AD patients with an ADAS-Cog score between 20 and 46, we retested their ADAS-Cog score 1 year later. The levels of docosahexaenoic acid plasmalogen were measured by use of liquid chromatography-tandem mass spectrometry. Results: We found that the ADAS-Cog score increased significantly in AD patients with circulating plasmalogen levels that were ≤ 75% of that of age-matched controls at entry into the study. There was no change in score among participants with normal serum plasmalogen levels at baseline (> 75%). Limitations: This was a pilot study with 40 patients, and the results require validation in a larger population. Conclusion: Our study demonstrates that decreased levels of plasmalogen precursors in the central nervous system correlate with functional decline (as measured by ADAS-Cog scores) in AD patients. The use of both ADAS-Cog and serum plasmalogen data may be a more accurate way of predicting cognitive decline in AD patients, and may be used to decrease the risk of including patients with no cognitive decline in the placebo arm of a drug trial.

Plasmalogen Deficit: A New and Testable Hypothesis for the Etiology of Alzheimer’s Disease

“…It has long been known that peripheral sources of DHA lipids are critical for brain and retinal function (Scott and Bazan, 2007). The importance of these observations has been highlighted by recent reports of decreased liver synthesis (Astarita et al, 2010) and circulating levels (Goodenowe et al, 2007) of DHA and DHA phospholipids in Alzheimer's disease, which correlate with cognitive decline and brain decrements in DHA-containing plasmalogens (Han et al, 2001;Goodenowe et al, 2007;Wood et al, 2010). Clearly a next step is to define the site or sites of phospholipid remodeling that allow restoration of myelin plasmalogens and phosphatidylethanolamines.…”

“…These data support the hypothesis that a peripheral decline in PlsEtn can cause CNS PlsEtn depletion. We have previously reported extensively on the role of plasmalogens in cognition and the association between serum DHA-PlsEtn levels and AD (Goodenowe et al, 2007;Wood et al, 2010). In brief, when compared to cognitively confirmed, age and gender-matched controls (MMSE 29-30, age 77+/-0.8, n=68), subjects with low (ADAS cog 5-19, age 79.3+/-0.8, n=78), moderate (ADAS cog 20-39, age 79.1+/-0.7, n=112), and severe (ADAS cog 40-70, age 82.1+/-1, n=66) dementia had increasingly lower levels of DHA-PlsEtn in their serum (74%, p=3.0e-4; 66%, p=1.3e-7; 53%, p=3.9e-11, respectively).…”

Lipidomics Analysis of Peroxisomal Disorders: Discovery of Deficits in Phosphatidyglycerol Levels in Rhizomelic Chondrodysplasia Type 1

“…Since it is the goal of a number of investigators to evaluate plasmalogen precursors as potential therapeutics for peroxisomal disorders [4,7], increasing in our knowledge base of the lipidome in RCDP will be very valuable for future translational research efforts. Furthermore, recognition of a peroxisomal deficit in Alzheimer's disease [8][9][10], which may underlie cerebral white matter dysmyelination in Alzheimer's disease [10][11][12], also support increasing our understanding of the full consequences of peroxisomal deficits on the human lipidome.…”

“…The clinical studies were approved by the Lincoln Memorial University Institutional Review Board. Plasma samples were processed as described previously, utilizing tert-butyl methylether and methanol for extraction of lipids [4][5][6]12] Extracts were dried by centrifugal vacuum evaporation and dissolved in isopropanol : methanol : chloroform 4:2:1 containing 7.5 mM ammonium acetate. Shotgun lipidomics were performed utilizing high-resolution (140,000 at 200 amu) data acquisition, with sub-ppm mass accuracy on an orbitrap mass spectrometer (Thermo Q Exactive) with successive switching between polarity modes [5,6].…”

Hydrolysis of plasmalogen by phospholipase A1 from Streptomyces albidoflavus for early detection of dementia and arteriosclerosis

“…Wood et al (2010) showed that ethanolamine plasmalogen (PlsEtn) levels in the serum declined in the early stage of Alzheimer-type dementia. Maeba et al (2007) showed a positive correlation between Pls and high-density lipoprotein and also demonstrated that serum Pls levels decrease with aging.…”