title: ApoE alleles and tau markers in patients with different levels of cognitive impairment.
abstract: BACKGROUND
  The presence of brain hyperphosphorylated tau constitutes a hallmark of neurodegenerative disorders of the Alzheimer's type. This report describes the relationships between tau markers in the cerebrospinal fluid (CSF), the degree of cognitive impairment and the predictive value of genetic markers such the alleles of apolipoprotein E, namely, the presence of Apo-epsilon4, as part of a longitudinal study.
  
  
  METHODS
  Three major groups of patients with ages ranging from 65-73 years were evaluated in this study (n=72): Alzheimer's disease patients (AD), a group with mild cognitive impairment (MCI) and normal senile patients (NS). Hyperphosphorylated tau and tau dephosphorylated species at the Alzheimer-type epitopes in CSF samples were analyzed by ELISA assays using a battery of different monoclonal antibodies. ApoE was analyzed by PCR in blood samples.
  
  
  RESULTS
  The levels of hyperphosphorylated tau were significantly higher in AD patients, but no statistical differences were found between the MCI and NS groups. However, the analysis of tau markers and cognitive impairment indicated the existence of two main subgroups within this population: MCI patients with a higher cognitive impairment as revealed by the total box score (TBS) >1.5 who exhibited phosphorylated tau patterns similar to the AD group, and patients with a mild impairment (TBS <1.5) with tau patterns similar to normal patients. In regard to ApoE, epsilon4/epsilon4 genotype was absent in the Chilean population analyzed, and only the epsilon2/epsilon4 genotype was significantly increased in both MCI and AD patients. A detailed analysis of the ApoE alleles, particularly epsilon3 and epsilon4, indicated a tendency to increase the epsilon4 allele in the MCI group with higher cognitive impairment and in AD patients.
  
  
  CONCLUSIONS
  Studies indicate that hyperphosphorylated tau is a good indicator of the degree of cognitive disorders in early stages of AD and that no clear correlation exists with the epsilon4/epsilon4 and epsilon3/epsilon4 genotypes, even though a higher proportion of epsilon4 allele in the MCI group with a more significant level of impairment and in AD patients was evidenced.
authors.affiliation: Department of Neurological Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Manuel
authors.initials: M
authors.lastname: Lavados
authors.forename: Gustavo
authors.initials: G
authors.lastname: Farías
authors.forename: Francisco
authors.initials: F
authors.lastname: Rothhammer
authors.forename: Marta
authors.initials: M
authors.lastname: Guillon
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mujica
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Maccioni
authors.forename: Ricardo B
authors.initials: RB
authors.lastname: Maccioni
mesh_terms: D000368:Aged; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D005819:Genetic Markers; D020033:Protein Isoforms; D016875:tau Proteins