SELECTIVE BINDING OF SOLUBLE A-BETA-1-40 AND A-BETA-1-42 TO A SUBSET OF SENILE PLAQUES

Alzheimer's disease is characterized by the progressive accumulation o f amyloid-beta protein (A beta) in senile plaques and cerebral amyloid angiopathy, It is not known whether the plaque growth is a continuous and homogeneous process or whether some plaques have a more rapid evo lution, As plaques grow by the deposition of A beta, we used an in sit u binding technique to analyze tbe deposition of fluorescein-conjugate d and biotinylated A beta 1-40 and A beta 1-42 in cryosections of brai ns from Alzheimer's disease patients, Only a subset of senile plaques but all cerebrovascular A beta deposits were labeled by both A beta 1- 40 and A beta 1-42, Striking differences in binding were observed amon g adjacent plaques, Quantitative analysis showed that on average 60% o f all plaques were labeled with A beta 1-42 and 31% of all plaques wer e labeled with A beta 1-40 (n = 7; P < 0.001), Confocal laser scanning microscopy of double-labeled sections revealed that the newly deposit ed A beta was only partially co-localized to pre-existing A beta and a polipoprotein E and was not co-localized to heparan sulfate proteoglyc an, A beta binding was preserved after glycolytic pretreatment with pe riodic acid, Our results suggest that at a given time point only a sub set of active senile plaques accumulate A beta and that plaque growth may be conditioned by the presence of other distinct plaque components different from A beta, apolipoprotein E or heparan sulfate proteoglyc an.