Maternal transmission of Alzheimer's disease: prodromal metabolic phenotype and the search for genes
Open accessAbstract
After advanced age, having a parent affected with Alzheimer's disease (AD) is the most significant risk factor for developing AD among cognitively normal (NL) individuals. Although rare genetic mutations have been identified among the early-onset forms of familial AD (EOFAD), the genetics of the more common forms of late-onset AD (LOAD) remain elusive. While some LOAD cases appear to be sporadic in nature, genetically mediated risk is evident from the familial aggregation of many LOAD cases. The patterns of transmission and biological mechanisms through which a family history of LOAD confers risk to the offspring are not known. Brain imaging studies using 2-[ (18) F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG PET) have shown that NL individuals with a maternal history of LOAD, but not with a paternal family history, express a phenotype characterised by a pattern of progressive reductions of brain glucose metabolism, similar to that in AD patients. As maternally inherited AD may be associated with as many as 20 per cent of the total LOAD population, understanding the causes and mechanisms of expression of this form of AD is of great relevance. This paper reviews known genetic mutations implicated in EOFAD and their effects on brain chemistry, structure and function; epidemiology and clinical research findings in LOAD, including in vivo imaging findings showing selective patterns of hypometabolism in maternally inherited AD; possible genetic mechanisms involved in maternal transmission of AD, including chromosome X mutations, mitochondrial DNA and imprinting; and genetic mechanisms involved in other neurological disorders with known or suspected maternal inheritance. The review concludes with a discussion of the potential role of brain imaging for identifying endophenotypes in NL individuals at risk for AD, and for directing investigation of potential susceptibility genes for AD.
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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 [131]
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 [131]
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Self-citation
- Authors
- Mosconi, L., Berti, V., Swerdlow, R. H., Pupi, A., Duara, R., & de Leon, M.
- Affiliations
- New York University (US)
- Azienda Ospedaliero-Universitaria Careggi (IT)
- University of Miami (US)
- Corresponding author
- Mosconi, Lisa
- Venue
- Human Genomics
- Published
- 2010
- Volume
- 4
- Issue
- 3
- Pages
- 170
- ISSN
- 1473-9542 (ISSN-L)
- 1479-7364
- PMC
- PMC3033750
- OpenAlex
- W1987500343
- Cited by
- 85
- References
- 182
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 9 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 7 · 2012: 8
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Human Genomics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AG08051)
- National Institute on Aging (R01AG022374, AG022407, R01AG022407, P30AG008051, AG032554, AG 08051, R21AG032554, P30AG035982, R01AG013616, R01AG035137, AG 13616)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, mother-to-child transmission, late-onset Alzheimer's disease, familial aggregation, brain glucose hypometabolism, 18F-FDG PET, endophenotypes, susceptibility genes, mitochondrial DNA, genomic imprinting, early-onset familial Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Brain Mapping, Humans, Mothers, Phenotype, Age of Onset, Radiopharmaceuticals, Fluorodeoxyglucose F18, Genetic Predisposition to Disease, Positron-Emission Tomography
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