Publication Type Academic Article
Authors Mosconi L, Rinne J, Tsui W, Berti V, Li Y, Wang H, Murray J, Scheinin N, Någren K, Williams S, Glodzik L, De Santi S, Vallabhajosula S, de Leon M
Journal Proc Natl Acad Sci U S A
Volume 107
Issue 13
Pagination 5949-54
Date Published 03/15/2010
ISSN 1091-6490
Keywords Alzheimer Disease, Amyloid, Amyloid beta-Peptides
Abstract 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.
DOI 10.1073/pnas.0914141107
PubMed ID 20231448
PubMed Central ID PMC2851906
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