Oxidative Stress and Amyloid-Beta Pathology in Normal Individuals with A Maternal History of Alzheimer's

Mosconi, Lisa; Glodzik, Lidia; Mistur, Rachel L.; McHugh, Pauline; Rich, Kenneth; Javier, Elizabeth; Williams, Schantel; Pirraglia, Elizabeth; Santi, Susan De; Mehta, Pankaj; Zinkowski, Raymond; Blennow, Kaj; Praticò, Domenico; Leon, Mony J. de

doi:10.1016/j.biopsych.2010.07.011

Cited by 41 publications

(37 citation statements)

References 63 publications

(71 reference statements)

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“…The relative consistency of these FH findings across diverse neuroimaging modalities 4,[7][8][9]11 suggests that FH is a prominent, even if nonspecific, risk factor for AD perhaps embodying an array of genetic and environmental indices that remain to be fully elucidated. 10,22 Contrary to prior reports suggesting that maternal history of AD might confer a greater risk of ADrelated cerebral abnormalities than paternal history of AD, 5,7,8,18,23 we found that pFHϩ subjects were just as likely as mFHϩ subjects to experience atrophy of the posterior hippocampus. This observation suggests that, in our cohort, the FH effect was not driven by a particular parent of origin.…”

Section: Results Demographic Findingscontrasting

confidence: 56%

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults

Okonkwo¹,

Xu²,

Dowling³

et al. 2012

Neurology

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Objective: To evaluate the longitudinal influence of family history (FH) of Alzheimer disease (AD) and apolipoprotein E ⑀4 allele (APOE4) on brain atrophy and cognitive decline over 4 years among asymptomatic middle-aged individuals.Methods: Participants were cognitively healthy adults with (FHϩ) (n ϭ 60) and without (FHϪ) (n ϭ 48) a FH of AD (mean age at baseline 54 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention. They underwent APOE genotyping, cognitive testing, and an MRI scan at baseline and 4 years later. A covariate-adjusted voxel-based analysis interrogated gray matter (GM) modulated probability maps at the 4-year follow-up visit as a function of FH and APOE4. We also examined the influence of parent of origin on GM atrophy. Parallel analyses investigated the effects of FH and APOE4 on cognitive decline.Results: Neither FH nor APOE4 had an effect on regional GM or cognition at baseline. Longitudinally, a FH ϫ APOE4 interaction was found in the right posterior hippocampus, which was driven by a significant difference between the FHϩ and FHϪ subjects who were APOE4Ϫ. In addition, a significant FH main effect was observed in the left posterior hippocampus. No significant APOE4 main effects were detected. Persons with a maternal history of AD were just as likely as those with a paternal history of AD to experience posterior hippocampal atrophy. There was no longitudinal decline in cognition within the cohort. Conclusion:Over a 4-year interval, asymptomatic middle-aged adults with FH of AD exhibit significant atrophy in the posterior hippocampi in the absence of measurable cognitive changes. This result provides further evidence that detectable disease-related neuroanatomic changes do occur early in the AD pathologic cascade. Neurology ® 2012;78:1769-1776 GLOSSARY AD ϭ Alzheimer disease; ANCOVA ϭ analysis of covariance; FH ϭ family history; GM ϭ gray matter; mFH ϭ maternal family history; MNI ϭ Montreal Neurological Institute; pFH ϭ paternal family history; WRAP ϭ Wisconsin Registry for Alzheimer's Prevention.

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Section: Results Demographic Findingscontrasting

confidence: 56%

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults

Okonkwo¹,

Xu²,

Dowling³

et al. 2012

Neurology

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“…Cerebrospinal fluid (CSF) analysis reveals a lower CSF Ab42/ Ab40 ratio and CSF isoprostanes, a marker of oxidative stress, are higher (186). On memory tests, APOE4 carriers with AD mothers do not perform as well as APOE4 carriers with AD fathers (69).…”

Section: Swerdlowmentioning

confidence: 97%

“…compound B (PIB) PET reveals a greater degree of Ab plaque deposition in those with AD mothers (186,188). Cerebrospinal fluid (CSF) analysis reveals a lower CSF Ab42/ Ab40 ratio and CSF isoprostanes, a marker of oxidative stress, are higher (186).…”

Section: Swerdlowmentioning

confidence: 99%

Mitochondria and Cell Bioenergetics: Increasingly Recognized Components and a Possible Etiologic Cause of Alzheimer's Disease

Swerdlow

2012

Antioxidants & Redox Signaling

171

184

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“…These studies include demonstrations of increased brain amyloid deposition in the cognitively intact children of AD mothers, increased isoprostanes and AD-like Aβ42 changes in cerebrospinal fluid from cognitively intact children of AD mothers, increased degrees and rates of brain atrophy in cognitively intact children of AD mothers, and a potential relative softening of memory test performance in cognitively intact children of AD mothers (Berti et al, 2011; Debette et al, 2009; Honea et al, 2011; Honea et al, 2010; Mosconi et al, 2010a; Mosconi et al, 2009; Mosconi et al, 2010b). …”

Section: Mitochondria In Admentioning

confidence: 99%

Role of mitochondrial homeostasis and dynamics in Alzheimer's disease

Selfridge

Lezi

et al. 2013

Neurobiology of Disease

145

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease that affects a staggering percentage of the aging population and causes memory loss and cognitive decline. Mitochondrial abnormalities can be observed systemically and in brains of patients suffering from AD, and may account for part of the disease phenotype. In this review, we summarize some of the key findings that indicate mitochondrial dysfunction is present in AD-affected subjects, including cytochrome oxidase deficiency, endophenotype data, and altered mitochondrial morphology. Special attention is given to recently described perturbations in mitochondrial autophagy, fission-fusion dynamics, and biogenesis. We also briefly discuss how mitochondrial dysfunction may influence amyloidosis in Alzheimer’s disease, why mitochondria are a valid therapeutic target, and strategies for addressing AD-specific mitochondrial dysfunction.

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Oxidative Stress and Amyloid-Beta Pathology in Normal Individuals with A Maternal History of Alzheimer's

Cited by 41 publications

References 63 publications

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults

Mitochondria and Cell Bioenergetics: Increasingly Recognized Components and a Possible Etiologic Cause of Alzheimer's Disease

Role of mitochondrial homeostasis and dynamics in Alzheimer's disease

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