TY - JOUR
T1 - The effect of MAPT H1 and APOE ε4 on transition from mild cognitive impairment to dementia
AU - Samaranch, Lluís
AU - Cervantes, Sebastián
AU - Barabash, Ana
AU - Alonso, Alvaro
AU - Cabranes, José Antonio
AU - Lamet, Isabel
AU - Ancín, Inés
AU - Lorenzo, Elena
AU - Martínez-Lage, Pablo
AU - Marcos, Alberto
AU - Clarimón, Jordi
AU - Alcolea, Daniel
AU - Lleó, Alberto
AU - Blesa, Rafael
AU - Gómez-Isla, Teresa
AU - Pastor, Pau
PY - 2010
Y1 - 2010
N2 - Microtubule-associated protein tau (MAPT) and apolipoprotein E (APOE) are involved in the pathogenic mechanisms of Alzheimer's disease (AD). We prospectively followed three longitudinal independent samples (total n=319) with amnestic mild cognitive impairment (MCI) and analyzed whether MAPT H1/H2 haplotypes and APOE ε4 polymorphisms accelerated the rate of progression from MCI to dementia. At the end of the study, 172 subjects remained cognitively stable, whereas 147 progressed to dementia. APOE ε4 and MAPT H1/H1 were independently associated with an increased rate of progression to dementia in the combined sample. Cox regression models of the combined MCI sample showed that MAPT H1/H1 carriers had an increased rate of progression to dementia compared with non carriers (Hazard Ratio =1.45; 95% CI=1.04-2.02; p=0.028) and time-to-progression was shortened by 1.37 years. APOE ε4 allele also accelerated progression to dementia (Hazard Ratio=1.47; 95% CI= 1.06-2.04; p=0.020) and reduced the time-to-progression by 0.87 years. Additionally, MAPT H1/H1 genotype and APOE ε4 allele had an additive effect in progression to dementia, increasing progression rate to dementia (Hazard Ratio=2.24, 95% CI =1.40-3.58; p=0.001) and shortening time-to-progression to dementia by 2.92 years. Similar results were obtained when only considering progression to AD-type dementia. Our results suggest that both MAPT H1/H1 genotype and APOE ε4 allele lead to a more rapid progression to dementia among MCI subjects, probably mediating an increased rate of amyloid-β and tau brain deposition.
AB - Microtubule-associated protein tau (MAPT) and apolipoprotein E (APOE) are involved in the pathogenic mechanisms of Alzheimer's disease (AD). We prospectively followed three longitudinal independent samples (total n=319) with amnestic mild cognitive impairment (MCI) and analyzed whether MAPT H1/H2 haplotypes and APOE ε4 polymorphisms accelerated the rate of progression from MCI to dementia. At the end of the study, 172 subjects remained cognitively stable, whereas 147 progressed to dementia. APOE ε4 and MAPT H1/H1 were independently associated with an increased rate of progression to dementia in the combined sample. Cox regression models of the combined MCI sample showed that MAPT H1/H1 carriers had an increased rate of progression to dementia compared with non carriers (Hazard Ratio =1.45; 95% CI=1.04-2.02; p=0.028) and time-to-progression was shortened by 1.37 years. APOE ε4 allele also accelerated progression to dementia (Hazard Ratio=1.47; 95% CI= 1.06-2.04; p=0.020) and reduced the time-to-progression by 0.87 years. Additionally, MAPT H1/H1 genotype and APOE ε4 allele had an additive effect in progression to dementia, increasing progression rate to dementia (Hazard Ratio=2.24, 95% CI =1.40-3.58; p=0.001) and shortening time-to-progression to dementia by 2.92 years. Similar results were obtained when only considering progression to AD-type dementia. Our results suggest that both MAPT H1/H1 genotype and APOE ε4 allele lead to a more rapid progression to dementia among MCI subjects, probably mediating an increased rate of amyloid-β and tau brain deposition.
KW - APOE
KW - Alzheimer's disease
KW - MAPT
KW - genetics
KW - interaction
KW - microtubule-associated tau protein
KW - mild cognitive impairment
UR - http://www.scopus.com/inward/record.url?scp=79751476762&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79751476762&partnerID=8YFLogxK
U2 - 10.3233/JAD-2010-101011
DO - 10.3233/JAD-2010-101011
M3 - Article
C2 - 20930301
AN - SCOPUS:79751476762
SN - 1387-2877
VL - 22
SP - 1065
EP - 1071
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -