The H1 haplotype of the tau gene (MAPT) is associated with mild cognitive impairment.
Mild cognitive impairment is often considered a transitional condition prodromal to Alzheimer's disease. The dissection of genetic risk factors predisposing to mild cognitive impairment is paramount to assess the individual predisposition and reliably evaluate the effectiveness of early therapeutic interventions. We designed a cross-sectional analysis to test whether the occurrence of mild cognitive impairment is influenced by variations of the tau protein gene. The genotypes of seven polymorphisms tagging the major tau haplotypes were assayed on 186 patients with amnestic mild cognitive impairment and 191 unrelated controls. Association study was conducted by logistic regression including APOE genotype and age as covariates. Case-control analysis showed that the common H1 haplotype is significantly overrepresented in patients (OR, 95% CI: 2.31, 1.52-3.51; p<0.001), whereas did not provide positive signals for any of the H1 sub-haplotypes that had been described as associated with Alzheimer inverted exclamation mark s disease. This finding was confirmed when the epsilon4 allele of the APOE gene was taken into account (OR, 95% CI: 2.319, 1.492-3.603; p<0.001). These results firstly suggest that the risk of mild cognitive impairment is influenced by tau protein gene variations and that mild cognitive impairment shares a common genetic background with Alzheimer's disease. They may help elucidating the genetic risk to cognitive decline and designing effective clinical trials.
Department of Neuroscience, University of Genova, Genova, Italy. emilio.dimaria@unige.it
Emilio
E
Di Maria
Sergio
S
Cammarata
Maria Isola
MI
Parodi
Roberta
R
Borghi
Luisa
L
Benussi
Marialaura
M
Galli
Daniela
D
Galimberti
Roberta
R
Ghidoni
Davide
D
Gonella
Cristina
C
Novello
Valeria
V
Pollero
Lucia
L
Perroni
Patrizio
P
Odetti
Elio
E
Scarpini
Giuliano
G
Binetti
Massimo
M
Tabaton
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics; D012720:Severity of Illness Index; D016875:tau Proteins / Q000235:genetics*
D001057:Apolipoproteins E; C054369:MAPT protein, human; D016875:tau Proteins