Antemortem-Postmortem Correlation of Florbetapir (18F) PET Amyloid Imaging with Quantitative Biochemical Measures of Aβ42 but not Aβ40
Antemortem-Postmortem Correlation of Florbetapir (18F) PET Amyloid Imaging with Quantitative Biochemical Measures of Aβ42 but not Aβ40
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DOI：
10.3233/jad-170762
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Roher, Alex E.
中科院分区：
文献类型：
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作者：
Beach, Thomas G.;Maarouf, Chera L.;Roher, Alex E.
淀粉样蛋白成像显示在老化的人脑中存在淀粉样β蛋白(Aβ)沉积，但仍不清楚Aβ的结构形式和修饰。在阿尔茨海默病中，大多数淀粉样沉淀物主要由以氨基酸残基Val40或Ala42结尾的Aβ组成。据报道，Aβ(40)主要局限于神经性斑块，而Aβ(42)可沉积在所有类型的淀粉样斑块中，并且通常是弥漫性斑块的唯一成分。这种区别很重要，因为它主要是与认知障碍相关的神经性斑块，而弥漫性斑块可能是Aβ沉积的初始类型。目前尚不清楚PET淀粉样配体，如florbetapir18F(AMYVID)对Aβ(40)或Aβ(42)的脑沉积是否具有部分或全部选择性。我们比较了55名受试者死前的florbetapir PET皮质/小脑信号强度(SUVR)与死后使用Aβ(40)和Aβ(42)特异性抗体进行的生化(ELISA)测量。Spearman的单变量相关性对于Aβ(40)和Aβ(42)都是显著的，但对于Aβ(42)来说更强。多元线性回归仅对Aβ有意义(42)。这些结果表明，florbetapir只与Aβ(40)结合很弱，如果有结合的话。这可能部分是由于Aβ(42)存在于贝塔折叠的片状三级结构中的可能性较高，或者是由于Aβ(40)和Aβ(42)在贝塔折叠的片状三级或四元结构中的差异。
Amyloid imaging demonstrates the in vivo presence of amyloid-beta (A beta) deposits in the aging human brain but it is still unknown which structural forms and modifications of A beta are detected. In Alzheimer's disease, most amyloid deposits are predominantly composed of A beta ending at amino acid residues Val40 or Ala42. It has been reported that A beta(40) is largely restricted to neuritic plaques while A beta(42) may be deposited in amyloid plaques of all types, and is often the sole component of diffuse plaques. The distinction is important as it is mainly the neuritic plaques that correlate with cognitive impairment while diffuse plaques may be the initial type of A beta deposited. Whether PET amyloid ligands such as florbetapir18F (Amyvid) are partially or wholly selective for brain deposits of A beta(40) or A beta(42) is currently unknown. We compared antemortem florbetapir PET cortical/cerebellar signal intensity (SUVr) of 55 subjects with postmortem biochemical (ELISA) measurements employing specific antibodies against A beta(40) and A beta(42). Spearman's univariable correlations were significant for both A beta(40) and A beta(42), but were much stronger for A beta(42). Multiple linear regression showed significance only for A beta(42). These results suggest that florbetapir binds only weakly, if at all, to A beta(40). This may be in part due to the higher likelihood for A beta(42) to be present in a beta-pleated sheet tertiary structure, or to differences between A beta(40) and A beta(42) in beta-pleated sheet tertiary or quaternary structure.