Aβ Plaque Density Research Articles

Biphenyls labeled with technetium 99m for imaging β-amyloid plaques in the brain

Formation and accumulation of excess aggregates of β-amyloid (Aβ) plaques in the brain are critical factors contributing to the development and progression of Alzheimer's disease (AD). There is an urgent need for in vivo imaging agents that can specifically demonstrate the location and density of Aβ plaques in the brain. The aim of this study was to develop potential technetium 99m ( 99mTc)-labeled diagnostic imaging agents specific for the detection of Aβ plaques. Based on previously obtained Aβ plaque-specific biphenyls containing a p- N, N-dimethylaminophenyl group, a series of 99mTc and Re–N 2S 2–biphenyl derivatives was prepared. The stable neutral and lipophilic 99mTc complexes, [ 99mTc] 19 and [ 99mTc] 23, A+B, were successfully obtained. As surrogates for the 99mTc complexes, the corresponding surrogates, Re complexes of 23, were also prepared. Surprisingly, it was found that the Re complexes showed distinctively different retention profiles as compared with the corresponding 99mTc complexes. Biodistribution studies indicated that [ 99mTc] 23A readily passed through the blood–brain barrier (1.18% dose/brain at 2 min) in contrast to the low brain penetration of [ 99mTc] 19 (0.29% dose/brain at 2 min). Initial results suggested that [ 99mTc] 23A showed selective binding to the Aβ plaque-like structures in the brain sections from transgenic mice but not in the postmortem human brain tissue of patients with confirmed AD. The results provide encouraging evidence that development of a 99mTc-labeled agent for imaging Aβ plaques in the brain may be feasible. Caution should be taken when comparing these 99mTc complexes with the corresponding surrogates — the Re complexes.

Beta-amyloid (Abeta)42(43), abeta42, abeta40 and apoE immunostaining of plaques in fatal head injury.

beta-Amyloid (Abeta) deposits are found in the brains of approximately one-third of patients who die within days after a severe head injury; their presence correlating strongly with possession of an apolipoprotein E (apoE)-epsilon4 allele. The aim of the study was to investigate the relationship between Abeta42, Abeta40 and apoE immunostaining of Abeta plaques in the cerebral cortex and the relevance of apoE genotype in 23 fatally head-injured patients. These cases were known to have Abeta deposits from a previous study in which they were examined and semiquantified and related to apoE genotype. In the present study, the temporal cortex was probed using four different antibodies that recognize Abeta42(43), Abeta40 and an antibody to apoE. Abeta42(43)-positive plaques were observed in all of the 23 cases and Abeta40 immunoreactivity in only 11 of the 23 cases. In addition, semiquantitative analysis showed that relatively fewer plaques were detected with anti-Abeta40 than anti-Abeta42(43). ApoE-immunoreactive plaques were identified in 18 of the 23 cases. The number of plaques stained for apoE was relatively less than for Abeta42(43) but greater than for Abeta40. Furthermore, the density of Abeta plaques detected using either Abeta42(43), Abeta40 or apoE antibodies was associated with possession of apoE-epsilon4 in an allele dose-dependent manner. The results are consistent with Abeta42(43) as the initially deposited species in brain parenchyma and provide evidence that apoE is involved in the early stages of amyloid deposition. Further, the findings may be of relevance to the role of apoE genotype in influencing outcome after acute brain injury.