Auriel A Willette1, Joseph L Webb2, Michael W Lutz3, Barbara B Bendlin4, Alexandra M Wennberg5, Jennifer M Oh4, Allen Roses3, Rebecca L Koscik6, Bruce P Hermann7, N Maritza Dowling8, Sanjay Asthana9, Sterling C Johnson9. 1. Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa, USA; Department of Psychology, Iowa State University, Ames, Iowa, USA; Department of Neurology, University of Iowa, Iowa City, Iowa, USA. Electronic address: Awillett@iastate.edu. 2. Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa, USA. 3. Bryan Alzheimer's Disease Research Center, Duke University, Durham, North Carolina, USA; Zinfandel Pharmaceuticals, Chapel Hill, North Carolina, USA. 4. Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, Wisconsin, USA; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. 5. Department of Health Sciences Research, Mayo Clinic (Rochester), Rochester, Minnesota, USA. 6. Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. 7. Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. 8. Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. 9. Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, Wisconsin, USA; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
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 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 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.
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 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 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 TOMM40poly-T length and AD-related decline.
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Authors: R C Mohs; D Knopman; R C Petersen; S H Ferris; C Ernesto; M Grundman; M Sano; L Bieliauskas; D Geldmacher; C Clark; L J Thal Journal: Alzheimer Dis Assoc Disord Date: 1997 Impact factor: 2.703
Authors: Auriel A Willette; Sterling C Johnson; Alex C Birdsill; Mark A Sager; Bradley Christian; Laura D Baker; Suzanne Craft; Jennifer Oh; Eric Statz; Bruce P Hermann; Erin M Jonaitis; Rebecca L Koscik; Asenath La Rue; Sanjay Asthana; Barbara B Bendlin Journal: Alzheimers Dement Date: 2014-07-17 Impact factor: 21.566
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Authors: Richard J Caselli; Amylou C Dueck; Matthew J Huentelman; Michael W Lutz; Ann M Saunders; Eric M Reiman; Allen D Roses Journal: Alzheimers Dement Date: 2012-11 Impact factor: 21.566
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