Increased fibrillar amyloid-β burden in normal individuals with a family history of late-onset Alzheimer’s
Open accessAbstract
Having a parent affected with late-onset Alzheimer's disease (LOAD) is a major risk factor among cognitively normal (NL) individuals. This (11)C-Pittsburgh Compound B (PiB)-PET study examines whether NL individuals with LOAD parents show increased fibrillar amyloid-beta (Abeta) deposition, a hallmark of Alzheimer's disease (AD) pathology and whether there are parent-of-origin effects. Forty-two 50- to 80-year-old NL persons were examined with PiB-PET. These individuals included 14 NL subjects with a maternal family history (FH) of LOAD (FHm), 14 NL subjects with a paternal FH (FHp), and 14 NL subjects with a negative family history of any dementia (FH-). Statistical parametric mapping and automated regions-of-interest were used to compare cerebral-to-cerebellar PiB standardized uptake value ratios, reflecting fibrillar Abeta burden, across groups. FH groups did not differ in age, gender, education, and apolipoprotein E (ApoE) status. NL FHm subjects showed higher PiB retention in AD-affected anterior and posterior cingulate cortex (PCC), precuneus, parietal, temporal, occipital, and frontal cortices, right basal ganglia, and thalamus, compared with FH- and FHp subjects. FHp subjects showed increased PiB retention in the PCC and frontal cortex, intermediate between FHm and FH- subjects. Results remained significant after controlling for age, gender, education, and ApoE status. Children of parents with LOAD, particularly those with affected mothers, have increased fibrillar Abeta load in AD-vulnerable regions compared with controls, perhaps accounting for the known increased risk for AD. Present findings may motivate further research on familial transmission and parent-of-origin effects in LOAD.
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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 [134]
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 [134]
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- Authors
- Mosconi, L., Rinne, J. O., Tsui, W. H., Berti, V., Li, Y., Wang, H., Murray, J., Scheinin, N., Någren, K., Williams, S., Glodzik, L., De Santi, S., Vallabhajosula, S., & de Leon, M. J.
- Affiliations
- New York University (US)
- University of Turku (FI)
- Nathan Kline Institute for Psychiatric Research (US)
- University of Florence (IT)
- New York University School of Medicine, New York, NY 10016;
- Weill Cornell Medicine (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-03-15
- Volume
- 107
- Issue
- 13
- Pages
- 5949-5954
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2851906
- OpenAlex
- W2158771218
- Cited by
- 135
- References
- 42
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 1 · 2020: 6 · 2019: 3 · 2018: 8 · 2017: 10 · 2016: 7 · 2015: 8 · 2014: 13 · 2013: 13 · 2012: 11
- FWCI
- 12.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- National Institute on Aging (AG022374, R01AG022374, P30AG008051, AG032554, R21AG032554, R01AG013616, AG 13616)
- National Center for Research Resources (M01RR0096, M01RR000096)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- late-onset Alzheimer's disease, familial risk, cognitively normal individuals, fibrillar amyloid-beta, amyloid-beta deposition, parent-of-origin effects, maternal family history, apolipoprotein E, family transmission, cingulate cortex, precuneus
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Aniline Compounds, Brain, Carbon Radioisotopes, Female, Humans, Male, Middle Aged, Thiazoles, Cohort Studies, Case-Control Studies, Amyloid beta-Peptides, Age of Onset, Radiopharmaceuticals, Positron-Emission Tomography, Benzothiazoles
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