Maternal Family History of Alzheimer’s Disease Predisposes to Reduced Brain Glucose Metabolism

Department of Psychiatry, New York University School of Medicine, 560 First Avenue, New York, NY 10016, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 11/2007; 104(48):19067-72. DOI: 10.1073/pnas.0705036104
Source: PubMed

ABSTRACT Having a parent affected with late-onset Alzheimer's disease (AD) is a risk factor for developing AD among cognitively normal subjects. We examined whether cognitively normal subjects with a parental family history of AD show cerebral metabolic rate of glucose (CMRglc) reductions consistent with AD as compared with those without a family history and whether there are parent gender effects. Forty-nine 50- to 80-year-old normal subjects were examined who received clinical, neuropsychological, and 2-[(18)F]fluoro-2-deoxy-d-glucose-positron emission tomography examinations, including 16 subjects with a maternal (FHm) and eight with a paternal (FHp) family history of AD and 25 with no family history (FH(-)). FH groups were comparable for demographic and neuropsychological measures. As compared with both FH(-) and FHp groups, FHm subjects showed CMRglc reductions in the same regions as clinically affected AD patients, involving the posterior cingulate cortex/precuneus, parietotemporal and frontal cortices, and medial temporal lobes (P < 0.05, corrected for multiple comparisons). These effects remained significant after accounting for possible risk factors for AD, including age, gender, education, apolipoprotein E genotype, and subjective memory complaints. No CMRglc differences were found between FHp and FH(-) subjects. This study shows a relationship between reduced CMRglc in AD-vulnerable brain regions and a maternal family history of AD in cognitively normal individuals.

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Available from: Miroslaw Brys, Jan 29, 2015
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    • "Indeed, unknown genegene and gene-environment interactions are likely to modulate the effect of this genetic factor on brain structure and function, potentially resulting in both overestimation and masking of APOE4 effects (see Donix et al. 2012 for review). In this respect, APOE genotype and family history risk were shown to have independent and/or additive contributions to brain structure (Donix et al. 2010b; Honea et al. 2010, 2011) or metabolism (Mosconi et al. 2007, 2009). "
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    • "Individuals classified as family history positive scored at or above age-and educationadjusted norms on the MoCA and reported either a maternal (n = 6), multiple (n = 6), or early-onset (n = 2) family history of AD. Paternal family history alone was not included in the high AD risk classification based on recent evidence that paternal history may not carry the same increased risk as maternal history [36] [37] [38]. "
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    • "Family history studies also support a role for mitochondrial dysfunction in AD. In contrast to nuclear DNA, mitochondrial DNA is inherited maternally, and both specific mitochondrial haplotypes and maternal family history are linked to AD-related structural, cognitive, CSF, and metabolic biomarkers [173] [174] [175] [176]. These findings of increased ADrelated change in maternal lines of AD suggest that transmission of risk is preferentially found in maternal inheritance. "
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