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[P‐133]: MR spectroscopy demonstrates presymptomatic changes in familial Alzheimer's disease
Author(s) -
Godbolt Alison K.,
MacManus David G.,
Waldman Adam D.,
Schott Jonathan M.,
Cipolotti Lisa,
Frost Chris,
Fox Nick C.,
Rossor Martin N.
Publication year - 2005
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.2005.06.206
Subject(s) - posterior cingulate , metabolite , medicine , voxel , pathological , nuclear medicine , presenilin , gastroenterology , magnetic resonance imaging , neuropsychology , pathology , alzheimer's disease , disease , radiology , psychiatry , functional magnetic resonance imaging , cognition
the majority of whom recovered to baseline. Autopsy data is available from 4 cases from the AN-1792 trial. Most of these cases were remarkable in that they showed very few plaques in at least some cortical areas that typically have a heavy amyloid load; implying an amyloid-clearing effect. This conclusion is blurred by the absence of a pre-treatment measure of amyloid load and emphasizes the importance of in vivo assessment of amyloid deposition both before and after anti-amyloid treatment. Our group has developed a PET tracer, known as Pittsburgh Compound-B (PIB), which appears to provide a good measure of amyloid deposition in living human brain. Objective(s): Determine whether PIB binding to post-mortem brain homogenates can differentiate AN-1792-treated AD brain from untreated AD brains and whether this correlates to the histopathology in the samples. Methods: Frozen samples of frontal, temporal and parietal cortex and cerebellum from control brains (n 4), AD brains (n 5) and from two brains from the AN-1792 trial were obtained (Ferrer and Masliah published cases). Brain samples were homogenized in PBS, incubated with 1 nM [H-3]PIB, filtered, washed and counted to determine bound [H-3]PIB. Near adjacent sections were processed for immunohistochemistry for A . Neuropathologically, these brains were remarkable for a focal absence of plaques in several cortical areas. In cortical areas, PIB binding was significantly lower in some areas of AN-1792 post-mortem brains and low PIB binding was related to low amyloid load determined by immunohistochemistry. In some cases, PIB binding in cortical areas of AN-1792-treated brains appeared reduced to control levels. Conclusions: The binding of PIB is markedly decreased by AN-1792 treatment. It appears likely that preand post-treatment in vivo amyloid imaging with PIB PET will be able to detect changes in brain amyloid produced by immunotherapies (active or passive).