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Increased fibrillar amyloid-{beta} burden in normal individuals with a family history of late-onset Alzheimer's.

TitleIncreased fibrillar amyloid-{beta} burden in normal individuals with a family history of late-onset Alzheimer's.
Publication TypeJournal Article
Year of Publication2010
AuthorsMosconi L, Rinne JO, Tsui WH, Berti V, Li Y, Wang H, Murray J, Scheinin N, NĂ¥gren K, Williams S, Glodzik L, De Santi S, Vallabhajosula S, de Leon MJ
JournalProc Natl Acad Sci U S A
Volume107
Issue13
Pagination5949-54
Date Published2010 Mar 30
ISSN1091-6490
KeywordsAge of Onset, Aged, Alzheimer Disease, Amyloid, Amyloid beta-Peptides, Benzothiazoles, Brain, Carbon Radioisotopes, Case-Control Studies, Cohort Studies, Female, Humans, Male, Middle Aged, Positron-Emission Tomography, Radiopharmaceuticals
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.

DOI10.1073/pnas.0914141107
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID20231448
PubMed Central IDPMC2851906
Grant ListR01 AG022374 / AG / NIA NIH HHS / United States
M01 RR000096 / RR / NCRR NIH HHS / United States
R21 AG032554 / AG / NIA NIH HHS / United States
R01 AG013616 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
AG022374 / AG / NIA NIH HHS / United States
AG032554 / AG / NIA NIH HHS / United States
AG13616 / AG / NIA NIH HHS / United States
M01RR0096 / RR / NCRR NIH HHS / United States

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