Reduced CSF PLTP activity in Alzheimer's disease and other neurologic diseases; PLTP induces ApoE secretion in primary human astrocytes in vitro

Simona Vuletic, Elaine R. Peskind, Santica M. Marcovina, Joseph Quinn, Marian C. Cheung, Hal Kennedy, Jeffrey Kaye, Lee Way Jin, John J. Albers

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Phospholipid transfer protein (PLTP) plays a pivotal role in cellular lipid efflux and modulation of lipoprotein metabolism. PLTP is distributed widely in the central nervous system (CNS), is synthesized by glia and neurons, and is active in cerebrospinal fluid (CSF). The aims of this study were to test the hypothesis that patients with Alzheimer's disease (AD) have altered PLTP-mediated phospholipid transfer activity in CSF, and to examine the potential relationship between PLTP activity and apolipoprotein E (apoE) levels in CSF. We assessed PLTP activity and apoE concentration in CSF of patients with probable AD (n = 50), multiple sclerosis (MS; n = 9), other neurologic diseases (n = 21), and neurologically healthy controls (n = 40). PLTP activity in AD was reduced compared to that in controls (P <0.001), with approximately half of the AD patients with PLTP activity values below all controls. Patients with MS had lower PLTP activity than AD patients (P <0.001). PLTP activity was highly correlated with PLTP mass, as estimated by Western blot (r = 0.006; P <0.01). CSF PLTP activity positively correlated with apoE concentration in AD (R = 0.435; P = 0.002) and controls (R = 0.456; P = 0.003). Anti-apoE immunoaffinity chromatography and Western blot analyses indicated that some CSF PLTP is associated with apoE-containing lipoproteins. Exogenous addition of recombinant PLTP to primary human astrocytes significantly increased apoE secretion to the conditioned medium. The findings of reduced PLTP activity in AD CSF, and the observation that PLTP can influence apoE secretion in astrocytes suggest a potential link between alterations in the brain lipid metabolism and AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)406-413
Number of pages8
JournalJournal of Neuroscience Research
Volume80
Issue number3
DOIs
StatePublished - May 1 2005
Externally publishedYes

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Phospholipid Transfer Proteins
Cerebrospinal Fluid Proteins
Apolipoproteins E
Nervous System Diseases
Astrocytes
Alzheimer Disease
Cerebrospinal Fluid
In Vitro Techniques
Lipoproteins
Western Blotting

Keywords

  • Alzheimer's disease
  • Cerebrospinal fluid
  • Lipoproteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Reduced CSF PLTP activity in Alzheimer's disease and other neurologic diseases; PLTP induces ApoE secretion in primary human astrocytes in vitro. / Vuletic, Simona; Peskind, Elaine R.; Marcovina, Santica M.; Quinn, Joseph; Cheung, Marian C.; Kennedy, Hal; Kaye, Jeffrey; Jin, Lee Way; Albers, John J.

In: Journal of Neuroscience Research, Vol. 80, No. 3, 01.05.2005, p. 406-413.

Research output: Contribution to journalArticle

Vuletic, Simona ; Peskind, Elaine R. ; Marcovina, Santica M. ; Quinn, Joseph ; Cheung, Marian C. ; Kennedy, Hal ; Kaye, Jeffrey ; Jin, Lee Way ; Albers, John J. / Reduced CSF PLTP activity in Alzheimer's disease and other neurologic diseases; PLTP induces ApoE secretion in primary human astrocytes in vitro. In: Journal of Neuroscience Research. 2005 ; Vol. 80, No. 3. pp. 406-413.
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AU - Quinn, Joseph

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AB - Phospholipid transfer protein (PLTP) plays a pivotal role in cellular lipid efflux and modulation of lipoprotein metabolism. PLTP is distributed widely in the central nervous system (CNS), is synthesized by glia and neurons, and is active in cerebrospinal fluid (CSF). The aims of this study were to test the hypothesis that patients with Alzheimer's disease (AD) have altered PLTP-mediated phospholipid transfer activity in CSF, and to examine the potential relationship between PLTP activity and apolipoprotein E (apoE) levels in CSF. We assessed PLTP activity and apoE concentration in CSF of patients with probable AD (n = 50), multiple sclerosis (MS; n = 9), other neurologic diseases (n = 21), and neurologically healthy controls (n = 40). PLTP activity in AD was reduced compared to that in controls (P <0.001), with approximately half of the AD patients with PLTP activity values below all controls. Patients with MS had lower PLTP activity than AD patients (P <0.001). PLTP activity was highly correlated with PLTP mass, as estimated by Western blot (r = 0.006; P <0.01). CSF PLTP activity positively correlated with apoE concentration in AD (R = 0.435; P = 0.002) and controls (R = 0.456; P = 0.003). Anti-apoE immunoaffinity chromatography and Western blot analyses indicated that some CSF PLTP is associated with apoE-containing lipoproteins. Exogenous addition of recombinant PLTP to primary human astrocytes significantly increased apoE secretion to the conditioned medium. The findings of reduced PLTP activity in AD CSF, and the observation that PLTP can influence apoE secretion in astrocytes suggest a potential link between alterations in the brain lipid metabolism and AD pathogenesis.

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