Phospholipid Abnormalities in Early Alzheimer's Disease

Cuénod, Charles‐André; Kaplan, David B.; Michot, Jean–Luc; Jehenson, P.; Leroy-Willig, A.; Forette, Françoise; Syrota, A.; Boiler, François

doi:10.1001/archneur.1995.00540250097018

Cited by 43 publications

(21 citation statements)

References 21 publications

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“…The PME levels inversely correlate with the Mattis score, which suggests that PME levels are highest at (or prior to) the onset of dementia (F 9). A recent 31 P MRS study of early AD subjects by another group of investigators also found elevated levels of PME in the early stage of AD 76 . Other in vivo 31 P MRS studies of AD brain regions from whole axial cross‐sectional slices through the corpus callosal white matter and lateral cerebral ventricles found no significant differences in the concentrations of phospholipid membrane metabolites 77,78 .…”

Section: Resultsmentioning

confidence: 87%

“…Other in vivo 31 P MRS studies of AD brain regions from whole axial cross‐sectional slices through the corpus callosal white matter and lateral cerebral ventricles found no significant differences in the concentrations of phospholipid membrane metabolites 77,78 . This inconsistency probably arises from differences in technique and the regions of the AD brain examined (i.e., a smaller volume of predominantly grey matter in the prefrontal cortex 56,76 versus a cross‐sectional axial slice through a larger volume of predominantly white matter and cerebral spinal fluid) 77,78 . In the 31 P MRS study by Bottomley et al , 77 the AD subjects and control subjects were not age‐matched, and although the PME levels were elevated by the same relative amount, a higher variance of the experimental data prevented this increase from reaching statistical significance.…”

Section: Resultsmentioning

confidence: 94%

“…The alterations in phospholipid metabolism detected in the 31 P MRS examination of postmortem AD tissue also are detectable by in vivo 31 P MRS 56,75,76 . An in vivo 31 P MRS investigation of the frontal and temporoparietal regions of AD subjects, multiple subcortical cerebral infarction (MSID) subjects, and age‐matched controls found significant elevations of PME levels in the temporoparietal region of AD brain compared to either controls or MSID subjects 75 .…”

Section: Resultsmentioning

confidence: 96%

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Magnetic Resonance Spectroscopic Changes in Alzheimer's Disease^a

Pettegrew

Klunk

Panchalingam

et al. 1997

Annals of the New York Academy of Sciences

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In vitro and in vivo 31P magnetic resonance (MR) spectroscopy studies of Alzheimer's disease (AD) brain have revealed alterations in membrane phospholipid metabolism and high-energy phosphate metabolism. Mildly demented AD patients compared with control subjects have increased levels of phosphomonoesters, decreased levels of phosphocreatine and probably adenosine diphosphate and an increased oxidative metabolic rate. As the dementia worsens, levels of phosphomonoesters decrease and levels of phosphocreatine and adenosine di-phosphate increase. The changes in oxidative metabolic rate suggest that the AD brain is under energetic stress. The phosphomonoester findings support our in vitro findings and implicate basic defects in membrane metabolism in AD brain. MR spectroscopy provides new diagnostic insights and a noninvasive method to follow the progression of the disease and the metabolic response to therapeutic interventions.

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Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 96%

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Magnetic Resonance Spectroscopic Changes in Alzheimer's Disease^a

Pettegrew

Klunk

Panchalingam

et al. 1997

Annals of the New York Academy of Sciences

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“…There also is solid evidence for a fundamental alteration in membrane phospholipid composition and metabolism in AD. [111][112][113][114][115][116][117][118][119] Of considerable importance is the observation that the membrane molecular changes actually precede cognitive decline. 120 In addition, there is in vivo evidence that ALCAR can reverse these membrane molecular and metabolic changes in some AD subjects.…”

Section: Restoration Of Cell Membranesmentioning

confidence: 99%

Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression

2000

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Acetyl-L-carnitine (ALCAR) contains carnitine and acetyl moieties, both of which have neurobiological properties. Carnitine is important in the ␤-oxidation of fatty acids and the acetyl moiety can be used to maintain acetyl-CoA levels. Other reported neurobiological effects of ALCAR include modulation of: (1) brain energy and phospholipid metabolism; (2) cellular macromolecules, including neurotrophic factors and neurohormones; (3) synaptic morphology; and (4) synaptic transmission of multiple neurotransmitters. Potential molecular mechanisms of ALCAR activity include: (1) acetylation of -NH 2 and -OH functional groups in amino acids and N terminal amino acids in peptides and proteins resulting in modification of their structure, dynamics, function and turnover; and (2) acting as a molecular chaperone to larger molecules resulting in a change in the structure, molecular dynamics, and function of the larger molecule. ALCAR is reported in double-blind controlled studies to have beneficial effects in major depressive disorders and Alzheimer's disease (AD), both of which are highly prevalent in the geriatric population. Molecular Psychiatry (2000) 5, 616-632.

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“…Abnormal membrane breakdown and/or turnover has been implicated in several human brain disorders including Alzheimer's disease (2,3), cerebral ischemia (4,5), schizophrenia (6)(7)(8), and cerebellar ataxia (9,10). This has prompted some investigators to consider the use of inhibitors of membrane breakdown or stimulators of membrane synthesis as potential therapeutic agents in these diseases.…”

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confidence: 99%

Phospholipid biosynthetic enzymes in human brain

Ross

Moszczynska²,

Blusztajn

et al. 1997

Lipids

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Growing evidence suggests an involvement of brain membrane phospholipid metabolism in a variety of neurodegenerative and psychiatric conditions. This has prompted the use of drugs (e.g., CDPcholine) aimed at elevating the rate of neural membrane synthesis. However, no information is available regarding the human brain enzymes of phospholipid synthesis which these drugs affect. Thus, the objective of our study was to characterize the enzymes involved, in particular, whether differences existed in the relative affinity of substrates for the enzymes of phosphatidylethanolamine (PE) compared to those of phosphatidylcholine (PC) synthesis. The concentration of choline in rapidly frozen human brain biopsies ranged from 32-186 nmol/g tissue, a concentration similar to that determined previously for ethanolamine. Since human brain ethanolamine kinase possessed a much lower affinity for ethanolamine (Km = 460 microM) than choline kinase did for choline (Km = 17 microM), the activity of ethanolamine kinase in vivo may be more dependent on substrate availability than that of choline kinase. In addition, whereas ethanolamine kinase was inhibited by choline, and to a lesser extent by phosphocholine, choline kinase activity was unaffected by the presence of ethanolamine, or phosphoethanolamine, and only weakly inhibited by phosphocholine. Phosphoethanolamine cytidylyltransferase (PECT) and phosphocholine cytidylyltransferase (PCCT) also displayed dissimilar characteristics, with PECT and PCCT being located predominantly in the cytosolic and particulate fractions, respectively. Both PECT and PCCT exhibited a low affinity for CTP (Km approximately 1.2 mM), suggesting that the activities of these enzymes, and by implication, the rate of phospholipid synthesis, are highly dependent upon the cellular concentration of CTP. In conclusion our data indicate different regulatory properties of PE and PC synthesis in human brain, and suggest that the rate of PE synthesis may be more dependent upon substrate (ethanolamine) availability than that of PC synthesis.

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Phospholipid Abnormalities in Early Alzheimer's Disease

Cited by 43 publications

References 21 publications

Magnetic Resonance Spectroscopic Changes in Alzheimer's Disease^a

Magnetic Resonance Spectroscopic Changes in Alzheimer's Disease^a

Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression

Phospholipid biosynthetic enzymes in human brain

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Phospholipid Abnormalities in Early Alzheimer's Disease

Cited by 43 publications

References 21 publications

Magnetic Resonance Spectroscopic Changes in Alzheimer's Diseasea

Magnetic Resonance Spectroscopic Changes in Alzheimer's Diseasea

Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression

Phospholipid biosynthetic enzymes in human brain

Contact Info

Product

Resources

About

Magnetic Resonance Spectroscopic Changes in Alzheimer's Disease^a

Magnetic Resonance Spectroscopic Changes in Alzheimer's Disease^a