TY - JOUR
T1 - Hemoglobin promotes Aβ oligomer formation and localizes in neurons and amyloid deposits
AU - Wu, Chih Wei
AU - Liao, Pao Chi
AU - Yu, Lung
AU - Wang, Shan Tair
AU - Chen, Shur Tzu
AU - Wu, Ching Ming
AU - Kuo, Yu Min
N1 - Funding Information:
This study was supported by grants from National Science Council (NSC92-2320-B-006-004) in Taiwan and National Institute on Aging (NIA Arizona ADCC, P30 AG019610). We thank Dr. Chao-Ching Huang for thoughtful discussions and Dr. Tyler A. Kokjohn for editing the manuscript.
PY - 2004/12
Y1 - 2004/12
N2 - The objective of this study was to search for brain-specific binding proteins that participated in Aβ aggregation. Immunoprecipitation of Aβ in Alzheimer's brain homogenate revealed a major co-precipitating 16-kDa protein band, which was identified through mass spectrometry as hemoglobin (Hb) α and β chains. Hemoglobin was distributed in Alzheimer's disease (AD) patients in a brain region-dependent manner, with the highest levels in the hippocampus and parietal gray (PG) matter, followed by parietal white matter (PW), and the lowest in cerebellum (Cb). AD parietal gray and white matters exhibited higher Hb levels than those in the nondemented (ND) group. Likewise, RT-PCR revealed that the Hb mRNA levels in AD inferior temporal gyri were higher than those of ND subjects. Furthermore, Hb was shown to promote Aβ oligomer formation. Immunohistochemical studies indicated that Hb was localized within the cytosol of pyramidal neurons in the hippocampus, suggesting a potential source of intracerebral Hb. Finally, double immunofluorescent assay confirmed the co-localization of Hb with senile plaques (SP) and cerebral amyloid angiopathy (CAA). We propose that an elevation in brain Hb via circulation leakage or perturbations of Hb gene regulation may participate in AD pathogenesis.
AB - The objective of this study was to search for brain-specific binding proteins that participated in Aβ aggregation. Immunoprecipitation of Aβ in Alzheimer's brain homogenate revealed a major co-precipitating 16-kDa protein band, which was identified through mass spectrometry as hemoglobin (Hb) α and β chains. Hemoglobin was distributed in Alzheimer's disease (AD) patients in a brain region-dependent manner, with the highest levels in the hippocampus and parietal gray (PG) matter, followed by parietal white matter (PW), and the lowest in cerebellum (Cb). AD parietal gray and white matters exhibited higher Hb levels than those in the nondemented (ND) group. Likewise, RT-PCR revealed that the Hb mRNA levels in AD inferior temporal gyri were higher than those of ND subjects. Furthermore, Hb was shown to promote Aβ oligomer formation. Immunohistochemical studies indicated that Hb was localized within the cytosol of pyramidal neurons in the hippocampus, suggesting a potential source of intracerebral Hb. Finally, double immunofluorescent assay confirmed the co-localization of Hb with senile plaques (SP) and cerebral amyloid angiopathy (CAA). We propose that an elevation in brain Hb via circulation leakage or perturbations of Hb gene regulation may participate in AD pathogenesis.
UR - https://www.scopus.com/pages/publications/9644302450
UR - https://www.scopus.com/pages/publications/9644302450#tab=citedBy
U2 - 10.1016/j.nbd.2004.08.014
DO - 10.1016/j.nbd.2004.08.014
M3 - Article
C2 - 15571973
AN - SCOPUS:9644302450
SN - 0969-9961
VL - 17
SP - 367
EP - 377
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -