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Lymphocyte-specific protein tyrosine kinase is a novel risk gene for Alzheimer disease

Wangtao Zhong1, Hidehisa D Yamagata, Keiko Taguchi

  • 1Department of Geriatric Medicine, Ehime University School of Medicine, Ehime, Japan.

Journal of the Neurological Sciences
|August 20, 2005
PubMed

Insights

Lymphocyte-specific protein tyrosine kinase (LCK) is a novel Alzheimer disease (AD) risk gene. A specific LCK gene variant (GG genotype) increases AD risk, independent of apolipoprotein E (APOE) status.

Area of Science:

  • Neuroscience
  • Genetics
  • Immunology

Background:

  • Lymphocyte-specific protein tyrosine kinase (LCK) is crucial for T-cell activation.
  • LCK is downregulated in Alzheimer disease (AD) hippocampus and located in an AD-associated genetic region.
  • LCK is a potential candidate gene for AD due to its biological role and genetic linkage.

Purpose of the Study:

  • To investigate the association between LCK gene polymorphisms and AD risk.
  • To examine the relationship between LCK, apolipoprotein E (APOE), and AD in a case-control study.

Main Methods:

  • Genotyping of a single nucleotide polymorphism (SNP) in LCK intron 1 (+6424 A/G).
  • Analysis included 376 AD patients (LOAD and EOAD) and 378 non-demented controls.
  • Statistical analysis included odds ratios (OR) and confidence intervals (CI), considering APOE genotype.

Main Results:

  • The LCK +6424 A/G polymorphism (GG genotype) was significantly associated with increased AD risk (OR=1.41 for total AD, OR=1.37 for LOAD).
  • APOE-epsilon4 significantly increased AD risk (OR=5.06).
  • The GG genotype of LCK remained a significant risk factor for AD even in APOE-epsilon4 non-carriers (OR=1.66).

Conclusions:

  • LCK represents a novel genetic risk factor for Alzheimer disease.
  • The identified LCK polymorphism contributes to AD susceptibility independently of APOE genotype.
  • These findings highlight LCK's potential role in AD pathogenesis.

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