High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types.
BACKGROUND
Supported by compelling genetic data regarding early-onset familial Alzheimer disease (AD), the amyloid beta-peptide (Abeta)-centric theory holds that Abeta is involved in the pathogenesis of sporadic AD. Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes lead to increased Abeta levels before symptoms arise.


OBJECTIVE
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 Abeta 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.


METHODS
Correlation analysis of positron emission tomography (PET) imaging studies.


METHODS
Academic research.


METHODS
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.


METHODS
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 Abeta burden was related to cognitive status.


CONCLUSIONS
Consistent with previous studies, the pattern of Abeta 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 Abeta deposition were not associated with mutation type nor cognitive status.
Villemagne
Victor L
VL
Department of Nuclear Medicine, Centre for Positron Emission Tomography, Austin Health, Heidelberg, Australia. villemagne@petnm.unimelb.edu.au
Ataka
Suzuka
S
Mizuno
Toshiki
T
Brooks
William S
WS
Wada
Yasuhiro
Y
Kondo
Masaki
M
Jones
Gareth
G
Watanabe
Yasuyoshi
Y
Mulligan
Rachel
R
Nakagawa
Masanori
M
Miki
Takami
T
Shimada
Hiroyuki
H
O'Keefe
Graeme J
GJ
Masters
Colin L
CL
Mori
Hiroshi
H
Rowe
Christopher C
CC
D000328:Adult; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics*; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics; D049268:Positron-Emission Tomography
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments