Genetic association of CDC2 with cerebrospinal fluid tau in Alzheimer's disease

We have recently reported that a polymorphism in the cell division
cycle (CDC2) gene, designated Ex6 + 7I/D, is associated with
Alzheimer's disease (AD). The CDC2 gene is located on chromosome
10q21.1 close to the marker D10S1225 linked to AD. Active cdc2
accumulates in neurons containing neurofibrillary tangles (NFT), a
process that can precede the formation of NFT. Therefore, CDC2 is a
promising candidate susceptibility gene for AD. We investigated the
possible effects of the CDC2 polymorphism on cerebrospinal fluid
(CSF) biomarkers in AD patients. CDC2 genotypes were evaluated in
relation to CSF protein levels of total tau, phospho-tau and
beta-amyloid (1-42) in AD patients and control individuals, and in
relation to the amount of senile plaques and NFT in the frontal
cortex and in the hippocampus in patients with autopsy-proven AD
and controls. The CDC2 Ex6 + 7I allele was associated with a gene
dose-dependent increase of CSF total tau levels (F-2,F- 626 = 7.0,
p = 0.001) and the homozygous CDC2Ex6 +7II genotype was
significantly more frequent among AD patients compared to controls
(p = 0.006, OR = 1.57, 95% CI 1.13-2.17). Our results provide
further evidence for an involvement of cdc2 in the pathogenesis of
AD. Copyright (C) 2005 S. Karger AG, Basel.