Dataset Information

Family history and TOMM40 '523 interactive associations with memory in middle-aged and Alzheimer's disease cohorts.

ABSTRACT: INTRODUCTION:Family history (FH) of Alzheimer's disease (AD) affects mitochondrial function and may modulate effects of translocase of the outer mitochondrial membrane 40 kDa (TOMM40) rs10524523 ('523) poly-T length on memory decline. METHODS:For 912 nonapolipoprotein ?4 middle-aged adults and 365 aged adults across the AD spectrum, linear mixed models gauged FH and TOMM40 '523 interactions on memory and global cognition between baseline and up to 10 years later. A cerebrospinal fluid mitochondrial function biomarker was also assessed. RESULTS:For FH negative participants, gene-dose preservation of memory and global cognition was seen for "very long" versus "short" carriers. For FH positive, an opposite gene-dose decline was seen for very long versus short carriers. Maternal FH was a stronger predictor in aged, but not middle-aged, participants. Similar gene-dose effects were seen for the mitochondrial biomarker aspartate aminotransferase. DISCUSSION:These results may clarify conflicting findings on TOMM40 poly-T length and AD-related decline.

SUBMITTER: Willette AA

PROVIDER: S-EPMC5810361 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Family history and TOMM40 '523 interactive associations with memory in middle-aged and Alzheimer's disease cohorts.

Willette Auriel A AA Webb Joseph L JL Lutz Michael W MW Bendlin Barbara B BB Wennberg Alexandra M AM Oh Jennifer M JM Roses Allen A Koscik Rebecca L RL Hermann Bruce P BP Dowling N Maritza NM Asthana Sanjay S Johnson Sterling C SC

Alzheimer's & dementia : the journal of the Alzheimer's Association 20170523 11

<h4>Introduction</h4>Family history (FH) of Alzheimer's disease (AD) affects mitochondrial function and may modulate effects of translocase of the outer mitochondrial membrane 40 kDa (TOMM40) rs10524523 ('523) poly-T length on memory decline.<h4>Methods</h4>For 912 nonapolipoprotein ε4 middle-aged adults and 365 aged adults across the AD spectrum, linear mixed models gauged FH and TOMM40 '523 interactions on memory and global cognition between baseline and up to 10 years later. A cerebrospinal f ...[more]

PMID: 28549947

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Project description:BackgroundParticulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases.ObjectivesIdentification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population.MethodsMicroarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM10 in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women). Pathway analysis was performed using Gene Set Enrichment Analysis. Average daily PM2.5 and PM10 exposures over 2-years were estimated for each participant's residential address using spatiotemporal interpolation in combination with a dispersion model.ResultsAverage long-term PM10 was 25.9 (± 5.4) and 23.7 (± 2.3) μg/m3 in the discovery and validation cohorts, respectively. In discovery analysis, associations between PM10 and the expression of individual genes differed by sex. In the validation cohort, long-term PM10 was associated with the expression of DNAJB5 and EAPP in men and ARHGAP4 (p = 0.053) in women. AKAP6 and LIMK1 were significantly associated with PM10 in women, although associations differed in direction between the discovery and validation cohorts. Expression of the eight candidate genes in the discovery cohort differentiated between validation cohort participants with high versus low PM10 exposure (area under the receiver operating curve = 0.92; 95% CI: 0.85, 1.00; p = 0.0002 in men, 0.86; 95% CI: 0.76, 0.96; p = 0.004 in women).ConclusionsExpression of the sex-specific candidate genes identified in the discovery population predicted PM10 exposure in an independent cohort of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects.

Dataset Information

Family history and TOMM40 '523 interactive associations with memory in middle-aged and Alzheimer's disease cohorts.

Publications

Family history and TOMM40 '523 interactive associations with memory in middle-aged and Alzheimer's disease cohorts.

Similar Datasets

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