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: 3.61). 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inflammation is observed in Alzheimer's disease (AD) subject brains. Inflammation-relevant genes are increasingly implicated in AD genetic studies, and inflammatory cytokines to some extent even function as peripheral biomarkers. What underlies AD inflammation is unclear, but no "foreign" agent has been implicated. This suggests that internally produced damage-associated molecular pattern (DAMPs) molecules may drive inflammation in AD. A more complete characterization and understanding of AD-relevant DAMPs could advance our understanding of AD and suggest novel therapeutic strategies. In this review, we consider the possibility that mitochondria, intracellular organelles that resemble bacteria in many ways, trigger and maintain chronic inflammation in AD subjects. Data supporting the possible nexus between AD-associated bioenergetic dysfunction are discussed.
    Frontiers in Aging Neuroscience 11/2014; 6:311. DOI:10.3389/fnagi.2014.00311 · 2.84 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer’s disease (AD) is a neurodegenerative disorder of the brain, inducing progressive severe presenile and senile cognitive decline, resulting in vegetative stage eventually. From the etiological point of view the main causative factor, remains unknown, in spite of the steady augmentation of the research efforts. Golgi staining revealed the substantial alterations of the dendritic branches and the tremendous loss of spines even in the initial stages of the disease. Electron microscopy reveals morphological changes of the mitochondria in neurons and astrocytes associated with fragmentation of cisternae of Golgi complex and pathological alteration of the dendritic spines, even in areas of the brain, which demonstrate minimal tau pathology and few amyloid β deposits. It is attempted to describe the ultrastructural alterations of the cerebellar cortex in early cases of AD, focusing the study mostly on mitochondria, Golgi apparatus, dendritic branches, dendritic spines and synapses in the cerebellar hemispheres and the vermis. Mitochondria demonstrated an impressive polymorphism in the soma, the axonal and dendritic profiles of Purkinje cells, the climbing fibers, the mossy fibers and the synapses. Electron microscopy revealed also marked fragmentation of cisternae of Golgi complex in large number of Purkinje cells, granule and stellate cells in the vermis and the cerebellar hemispheres. The fragmentation of the Golgi complex and the poverty in vesicles in cis- and trans-Golgi network in the soma of Purkinje cells in Alzheimer’s brains coincide with the synaptic loss, the shortage of the dendritic arborization and the pathological alterations of the spines. Numerous spines included large multivesicular bodies, altered spine apparatus, and unusual mitochondria. Giant elongated spines were seen in a substantial number of Purkinje cells. In many presynaptic terminals of parallel and mossy fibers, electron microscopy revealed a dramatic loss of the synaptic vesicles associated with marked polymorphism. On the basis of the mitochondrial and Golgi complex pathology, new therapeutic strategies protecting those organelles might be proposed for the treatment of early cases of AD.
    Frontiers in Clinical Drug Research - Alzheimer Disorders,, 1st edited by Atta-ur-Rahman, 12/2014: chapter 1: pages 3-27; Bentham Science Publishers., ISBN: 978-1-60805-871-6

Full-text (2 Sources)

Available from
May 21, 2014