Article

Maternal Family History is Associated with Alzheimer's Disease Biomarkers

KU Alzheimer's Disease Center, Department of Neurology, University of Kansas School of Medicine, Kansas City, KS 66160, USA.
Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 06/2012; 31(3):659-68. DOI: 10.3233/JAD-2012-120676
Source: PubMed

ABSTRACT

A family history of Alzheimer's disease (AD) increases one's risk of developing late-onset AD (LOAD), and a maternal family history of LOAD influences risk more than a paternal family history. Accumulating evidence suggests that a family history of dementia associates with AD-typical biomarker changes. We analyzed cross-sectional data from non-demented, mild cognitive impairment (MCI), and LOAD participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with PET imaging using Pittsburgh Compound B (PiB, n = 99) and cerebrospinal fluid (CSF) analysis (n = 403) for amyloid-β peptide (Aβ) and total tau. We assessed the relationship of CSF and PiB biomarkers and family history of dementia, as well as parent gender effects. In the larger analysis of CSF biomarkers, we assessed diagnosis groups individually. In the overall sample, CSF Aβ, tau/Aβ ratio, and global PiB uptake were significantly different between family history positive and negative groups, with markers of increased AD burden associated with a positive maternal family history of dementia. Moreover, a maternal family history of dementia was associated with significantly greater PiB Aβ load in the brain in the parietal cortex, precuneus, and sensorimotor cortex. Individuals with MCI positive for a maternal family history of dementia had significantly more markers of AD pathophysiology than individuals with no family history of dementia. A family history of dementia is associated with AD-typical biomarker changes. These biomarker associations are most robust in individuals with a maternal family history, suggesting that a maternally inherited factor influences AD risk.

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Available from: Russell Swerdlow, Apr 03, 2014
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    • "repair system , as well as the crucial role it plays in oxidative phosphorylation ( OXPHOS ) , render mtDNA a candidate to be the primary site of damage . mtDNA is inherited exclusively by maternal lineage and both mtDNA haplotypes and maternal family history are associated with cognitive and cerebrospinal fluid ( CSF ) biomarkers in AD patients ( Honea et al . , 2012 ; Ridge et al . , 2013 ) . Interestingly , mtDNA accumulates mutations throughout the aging process ( Michikawa et al . , 1999 ; Krishnan et al . , 2007 ) , which is indeed the main risk factor for AD ( Swerdlow et al . , 2014 ) . Here we shall explore different aspects of mitochondrial alterations found in AD patients , with special emp"
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