RESUMO
Insoluble alpha-synuclein plays a central role in Lewy body diseases, with considerable controversy as to whether it plays a similar role in Alzheimer's disease (AD). We assessed the tissue location and solubility of cortical alpha-synuclein in AD (without Lewy body formation) compared with controls, using sequential extraction procedures and Western immunoblotting to quantify different alpha-synuclein species in their different solubility states. Controls had no insoluble cortical alpha-synuclein and a ratio of soluble:lipid-associated alpha-synuclein of 1.2-/+0.1. Total alpha-synuclein protein was significantly increased in AD and concentrated within the lipid-associated fraction (soluble:lipid ratio 0.9-/+0.05, soluble:insoluble 1.5-/+0.1, lipid:insoluble 1.7-/+0.1) which proved difficult to localize in paraffin-embedded tissue. Tissues prepared without lipid extraction revealed alpha-synuclein-immunoreactivity in the amorphous components of mature cored AD plaques. This lipid-association of alpha-synuclein in mature AD plaques links this protein with other lipid changes thought to be important in disease pathogenesis.
Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Corpos de Lewy , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/biossíntese , Idoso , Idoso de 80 Anos ou mais , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Humanos , Corpos de Lewy/metabolismo , Corpos de Lewy/patologia , Masculino , Solubilidade , Sinucleínas , alfa-SinucleínaRESUMO
The cortical neurons thought to be selectively affected in dementia with Lewy bodies (DLB) are those containing nonphosphorylated 200-kDa neurofilament (NF) protein. As these neurons are largely spared in Alzheimer's disease (AD), DLB and AD may impact on different cortical neuronal populations. The present study quantifies the NF-containing neurons in frontal and temporal cortex of 8 AD, 8 DLB, and 8 control cases. Formalin-fixed paraffin-embedded tissue was immunohistochemically stained with antibodies against nonphosphorylated and phosphorylated NF. Immunoreactive neurons were quantified by areal fraction analysis and corrected for cortical volume. As expected, nonphosphorylated and phosphorylated NF accumulated in the pathological hallmarks of AD and DLB. However, rather than a decrease in NF-containing neurons, a doubling of this population was observed in DLB, compared with AD and controls. This increased number of cortical NF-containing neurons reveal novel widespread cortical changes, beyond those explained by Lewy body formation, that are specific for DLB.