Oxidative stress and amyloid-beta pathology in normal individuals with a maternal history of Alzheimer's
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Background Epidemiology and imaging studies showed that cognitively normal (NL) individuals with a maternal history (MH) of late-onset Alzheimer's disease (LOAD) might be at increased risk for Alzheimer's disease (AD) compared with NL with a paternal history (PH) and NL with a negative family history of LOAD (NH). With a panel of cerebrospinal fluid (CSF) markers, this study examined whether NL MH showed evidence for AD pathology compared with PH and NH.Methods Fifty-nine 40-80-year-old NL subjects were examined, including 23 MH and 14 PH whose parents had a clinician-certified diagnosis of LOAD and 22 NH. All subjects completed clinical neuropsychological examinations and a lumbar puncture to measure CSF levels of amyloid-beta (Aβ(40), Aβ(42), Aβ(42/40)), total and hyperphosphorylated tau (T-Tau and P-Tau(231); markers of axonal degeneration and neurofibrillary tangles, respectively), and F₂-isoprostanes (IsoP) (a marker of oxidative stress).Results Groups were comparable for demographic and neuropsychological measures. The MH subjects showed higher IsoP and reduced Aβ(42/40) CSF levels compared with NH and with PH (p values ≤ .05), whereas no differences were found between NH and PH. No group differences were found for P-Tau(231) and T-Tau. The IsoP and Aβ(42/40) levels were correlated only within the MH group (R² = .32, p = .005) and discriminated MH from the other subjects with 70% accuracy (relative risk = 3.7%, 95% confidence interval = 1.6-9.7, p < .001). Results remained significant controlling for age, gender, education, and apolipoprotein E genotype.Conclusions Adult children of LOAD-affected mothers express a pathobiological phenotype characterized by Aβ-associated oxidative stress consistent with AD, which might reflect increased risk for developing the disease.
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Cognitively intact children of AD mothers, relative to children of AD fathers, show greater age-associated brain atrophy, faster longitudinal brain atrophy, increased Aβ plaque deposition, elevated CSF oxidative stress markers, and AD-like CSF Aβ changes.
“Subsequent studies found that the cognitively intact children of AD mothers, relative to the cognitively intact children of AD fathers, show greater degrees of age-associated brain atrophy, faster rates of longitudinal brain atrophy, increased Aβ plaque deposition, elevated cerebrospinal fluid (CSF) oxidative stress markers, and AD-like CSF Aβ changes [130-137].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [132]
Maternal inheritance appears to determine several AD endophenotypes.
“Maternal inheritance appears to determine several AD endophenotypes.”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [132]
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Self-citation
- Authors
- Mosconi, L., Glodzik, L., Mistur, R., McHugh, P., Rich, K. E., Javier, E., Williams, S., Pirraglia, E., De Santi, S., Mehta, P. D., Zinkowski, R., Blennow, K., Pratico, D., & de Leon, M. J.
- Affiliations
- New York University (US)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Mosconi, Lisa
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 68
- Issue
- 10
- Pages
- 913-921
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2967599
- OpenAlex
- W1990202129
- Cited by
- 46
- References
- 69
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2020: 4 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 12
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health-National Institute on Aging (AG13616, AG12101, AG08051, AG022374, AG032554)
- National Institutes of Health-National Center for Research Resources (MO1RR0096)
- Alzheimer's Association
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Alzheimer's disease, maternal family history, cognitively normal individuals, oxidative stress, F2-isoprostanes, amyloid-beta, cerebrospinal fluid biomarkers, tau protein, neurofibrillary tangles, apolipoprotein E, disease risk
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Family Health, Female, Humans, Male, Middle Aged, Mothers, Biomarkers, Amyloid beta-Peptides, tau Proteins, Oxidative Stress, Genetic Predisposition to Disease, F2-Isoprostanes
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