High Striatal Amyloid beta-Peptide Deposition Across Different Autosomal Alzheimer Disease Mutation Types

作者：Villemagne Victor L^*; Ataka Suzuka; Mizuno Toshiki; Brooks William S; Wada Yasuhiro; Kondo Masaki; Jones Gareth; Watanabe Yasuyoshi; Mulligan Rachel; Nakagawa Masanori; Miki Takami; Shimada Hiroyuki; O'Keefe Graeme J; Masters Colin L; Mori Hiroshi; Rowe Christopher C

来源：Archives of Neurology, 2009, 66(12): 1537-1544.

DOI：10.1001/archneurol.2009.285

Background: Supported by compelling genetic data regarding early-onset familial Alzheimer disease (AD), the amyloid beta-peptide (A beta)-centric theory holds that A beta is involved in the pathogenesis of sporadic AD. Mutations in the amyloid precursor protein (APP), presenilin I (PSEN1), and presenilin 2 (PSEN2) genes lead to increased A beta levels before symptoms arise.
Objectives: To evaluate the pattern of Pittsburgh Compound B (PiB) retention in subjects with different autosomal dominant mutations associated with familial AD vs that in healthy age-matched control subjects and subjects with probable sporadic AD, to correlate A beta burden as measured by PiB with available clinical and cognitive data, and to compare the regional brain patterns of PiB retention and fluorodeoxyglucose F 18 (FDG) uptake.
Design: Correlation analysis of positron emission tomography (PET) imaging studies.
Setting: Academic research.
Participants: Seven PSEN1 mutation carriers and 1 APP mutation carrier underwent PiB and FDG PET imaging. Amyloid beta-peptide burden and FDG uptake were established using standardized uptake values normalized to pons.
Main Outcome Measure: Primary outcomes were PET results, which were compared with those of a well-characterized cohort of 30 healthy control subjects and 30 subjects with probable sporadic AD.
Results: All mutation carriers had high PiB retention in the striatum, with some also having cortical PiB retention in ventrofrontal and posterior cingulate/precuneus areas. The striatal pattern of PiB retention was similar in the PSEN1 and APP mutation carriers. Neither striatal nor cortical A beta burden was related to cognitive status.
Conclusions: Consistent with previous studies, the pattern of A beta deposition in familial AD differs from that in sporadic AD, with higher striatal and somewhat lower cortical PiB retention in familial AD. The pattern and degree of A beta deposition were not associated with mutation type nor cognitive status.

• 出版日期2009-12