Individuals with familial
Alzheimer's disease due to PSEN1 mutations develop high cortical fibrillar
amyloid-β load but often have lower cortical 11C-Pittsburgh compound B (PiB) retention than Individuals with sporadic
Alzheimer's disease. We hypothesized this is influenced by limited interactions of
Pittsburgh compound B with cotton wool plaques, an
amyloid-β plaque type common in familial
Alzheimer's disease but rare in sporadic
Alzheimer's disease. Histological sections of frontal and temporal cortex, caudate nucleus and cerebellum were obtained from 14 cases with sporadic
Alzheimer's disease, 12 cases with familial
Alzheimer's disease due to PSEN1 mutations, two relatives of a PSEN1 mutation carrier but without genotype information and three non-
Alzheimer's disease cases. Sections were processed immunohistochemically using
amyloid-β-targeting
antibodies and the fluorescent
amyloid stains cyano-PiB and
X-34. Plaque load was quantified by percentage area analysis. Frozen homogenates from the same brain regions from five sporadic
Alzheimer's disease and three familial
Alzheimer's disease cases were analysed for 3H-PiB in vitro binding and concentrations of amyloid-β1-40 and amyloid-β1-42. Nine sporadic
Alzheimer's disease, three familial
Alzheimer's disease and three non-
Alzheimer's disease participants had
11C-PiB PET with standardized uptake value ratios calculated using the cerebellum as the reference region. Cotton wool plaques were present in the neocortex of all familial
Alzheimer's disease cases and one sporadic
Alzheimer's disease case, in the caudate nucleus from four familial
Alzheimer's disease cases, but not in the cerebellum. Cotton wool plaques immunolabelled robustly with 4G8 and amyloid-β42
antibodies but weakly with amyloid-β40 and amyloid-βN3pE
antibodies and had only background cyano-PiB fluorescence despite labelling with
X-34. Relative to
amyloid-β plaque load, cyano-
Pittsburgh compound B plaque load was similar in sporadic
Alzheimer's disease while in familial
Alzheimer's disease it was lower in the neocortex and the caudate nucleus. In both regions, insoluble amyloid-β1-42 and amyloid-β1-40 concentrations were similar in familial
Alzheimer's disease and sporadic
Alzheimer's disease groups, while 3H-PiB binding was lower in the familial
Alzheimer's disease than the sporadic
Alzheimer's disease group. Higher amyloid-β1-42 concentration associated with higher 3H-PiB binding in sporadic
Alzheimer's disease but not familial
Alzheimer's disease.
11C-PiB retention correlated with region-matched post-mortem
amyloid-β plaque load; however, familial
Alzheimer's disease cases with abundant cotton wool plaques had lower
11C-PiB retention than sporadic
Alzheimer's disease cases with similar
amyloid-β plaque loads. PiB has limited ability to detect
amyloid-β aggregates in cotton wool plaques and may underestimate total
amyloid-β plaque burden in brain regions with abundant cotton wool plaques.