RESUMO
BACKGROUND/AIMS: A recent paper reported that the phospholipid transfer protein (PLTP) reduces phosphorylation of tau in human neuronal cells. In addition, patients with Alzheimer's disease (AD) have significantly higher levels of PLTP in brain tissue and significantly lower PLTP-mediated phospholipid transfer activity in cerebrospinal fluid. PLTP also affects apolipoprotein E (APOE) secretion from glial cells. This study aimed to investigate whether single nucleotide polymorphisms (SNPs) of the PLTP gene are associated with AD. METHODS: Five SNPs, genotyped using TaqMan technology, were analyzed using a case-control study design. Furthermore, we also checked for a synergetic association between the PLTP gene, APOE and AD. Our case-control dataset consisted of 180 AD patients and 130 age-matched controls. RESULTS: None of the SNPs showed a statistically significant association. We could not confirm any synergetic association between the SNPs and APOE in our AD patients. CONCLUSION: Our results indicate that there is no genetic association between PLTP and AD. Due to the relatively small sample size and the incomplete coverage of the region surrounding the PLTP gene of this study, larger genetic studies covering the entire PLTP gene region are needed.
Assuntos
Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Proteínas de Transferência de Fosfolipídeos/genética , Polimorfismo Genético/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Apolipoproteínas E/genética , Estudos de Casos e Controles , DNA/genética , Bases de Dados Genéticas , Feminino , Frequência do Gene , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Proteínas de Transferência de Fosfolipídeos/líquido cefalorraquidiano , Polimorfismo de Nucleotídeo Único , Análise de Regressão , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We assessed cerebrospinal fluid (CSF) levels of apolipoprotein E (apoE), phospholipid transfer protein (PLTP) activity, cholesterol, secreted amyloid-beta protein precursor alpha and beta (sAbetaPPalpha, sAbetaPPbeta), amyloid-beta peptides 1-40 (Abeta_{40}) and 1-42 (Abeta_{42}), total tau and tau phosphorylated at threonine 181 (pTau) in neurologically healthy, cognitively intact adults. ApoE significantly correlated with sAbetaPPalpha (r = 0.679), sAbetaPPbeta (r = 0.634), Abeta_{40} (r = 0.609), total and pTau (r = 0.589 and r = 0.673, respectively, all p < 0.001), PLTP activity (r = 0.242, p = 0.002) and cholesterol (r = 0.194, p < 0.01). PLTP activity significantly correlated with sAbetaPPalpha (r = 0.292), sAbetaPPbeta (r = 0.281), total and pTau (r = 0.265 and 0.258, respectively; all p Assuntos
Precursor de Proteína beta-Amiloide/líquido cefalorraquidiano
, Apolipoproteínas E/líquido cefalorraquidiano
, Proteínas tau/líquido cefalorraquidiano
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Envelhecimento/metabolismo
, Biomarcadores
, Colesterol/líquido cefalorraquidiano
, Feminino
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Degeneração Neural/líquido cefalorraquidiano
, Degeneração Neural/metabolismo
, Testes Neuropsicológicos
, Proteínas de Transferência de Fosfolipídeos/líquido cefalorraquidiano
, Valores de Referência
, Análise de Regressão
, Adulto Jovem
RESUMO
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.