Premium
O4‐07‐07: Longitudinal changes in fibrillar amyloid‐beta deposition across the cognitive spectrum: Effect of the APOE4 allele
Author(s) -
Cohen Ann,
Price Julie,
Mathis Chester,
Nebes Robert,
Saxton Judith,
Snitz Beth,
Aizenstein Howard,
Kamboh M.,
Lopez Oscar,
Weissfeld Lisa,
DeKosky Steven,
Klunk William
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.2018
Subject(s) - pittsburgh compound b , nuclear medicine , apolipoprotein e , alzheimer's disease , medicine , chemistry , psychology , disease
Background: The concept of preclinical Alzheimer’s disease (AD) implies that beta-amyloid (As) deposits may accumulate in the brain for a decade or more prior to the clinical manifestations of AD. The highest initial As deposition is observed in the precuneus. APOE e4 genotype is the major genetic susceptibility factor for AD associated with increased As deposition. In this longitudinal [C] PIB PET study, we compared regional rates of As accumulation in a large cohort of cognitively normal APOE e4 carriers (e4+) and non-carriers (e4-). Methods: One hundred forty six cognitively normal individuals (96 e4and 50 e4+ individuals; mean age 66 6 10 yo) underwent two [C] PIB scans, separated by 2.6 6 1.1 years. Regional binding potential (BP) values were estimated in manually derived MRI-based regions including precuneus, prefrontal, temporal, gyrus rectus, anterior cingulate, and occipital cortex and caudate nucleus. Mean cortical BP (MCBP) was calculated from the first four regions and used as a globalmeasure of brain As deposition (with 0.18 as a threshold level for abnormality). The rate of As accumulation was estimated from the annual change in BP.Results: In 115 of 146 individuals (85 e4and 30 e4+), As accumulation was low on both [C] PIB scans (Low-PIB), while 31 individuals (11 e4and 20 e4+) had elevated As accumulation on the second or both [C] PIB scans (High-PIB). The rate of As accumulation in the precuneus was significantly higher in the group of 50 e4+ individuals compared to 96 e4individuals (0.024 + 0.040 BP/year for e4+ and 0.011 + 0.036 BP/ year for e4-, p 1⁄4 0.044, two-tailed unpaired t-test). It also was higher in High-PIB (0.054 + 0.039 BP/year for e4+ and 0.016 + 0.028 BP/year for e4-, p 1⁄4 0.008, two-tailed unpaired t-test), but not in Low-PIB individuals. The other brain regions evaluated did not demonstrate significant changes in the rate of As accumulation between e4+ and e4individuals.Conclusions: In cognitively normal APOE e4 carriers the rate of As accumulation is significantly increased in the precuneus, indicating greater vulnerability of this cortical region at the early stage of AD pathology.