RGD Reference Report - The effect of MAPT H1 and APOE epsilon4 on transition from mild cognitive impairment to dementia. - Rat Genome Database

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The effect of MAPT H1 and APOE epsilon4 on transition from mild cognitive impairment to dementia.

Authors: Samaranch, L  Cervantes, S  Barabash, A  Alonso, A  Cabranes, JA  Lamet, I  Ancin, I  Lorenzo, E  Martinez-Lage, P  Marcos, A  Clarimon, J  Alcolea, D  Lleo, A  Blesa, R  Gomez-Isla, T  Pastor, P 
Citation: Samaranch L, etal., J Alzheimers Dis. 2010;22(4):1065-71. doi: 10.3233/JAD-2010-101011.
RGD ID: 10412700
Pubmed: PMID:20930301   (View Abstract at PubMed)
DOI: DOI:10.3233/JAD-2010-101011   (Journal Full-text)

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 epsilon4 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 epsilon4 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 epsilon4 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 epsilon4 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 epsilon4 allele lead to a more rapid progression to dementia among MCI subjects, probably mediating an increased rate of amyloid-beta and tau brain deposition.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dementia disease_progressionIAGP 10412700DNA:haplotype: :RGD 
dementia disease_progressionISOMAPT (Homo sapiens)10412700; 10412700DNA:haplotype: :RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mapt  (microtubule-associated protein tau)

Genes (Mus musculus)
Mapt  (microtubule-associated protein tau)

Genes (Homo sapiens)
MAPT  (microtubule associated protein tau)


Additional Information