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Updated: Aug 1, 2026
10:48
SDS-PAGE/Immunoblot Detection of Aβ Multimers in Human Cortical Tissue Homogenates using Antigen-Epitope Retrieval
Published on: April 23, 2010
Abnormal processing of multiple proteins in Alzheimer disease.
H Zhang1, N H Sternberger, L J Rubinstein
1Department of Neurology, University of Maryland School of Medicine, Baltimore 21201.
Summary
Neurofilaments are confirmed constituents of Alzheimer disease tangles, exceeding tau protein concentration. This challenges previous assumptions and suggests abnormal protein processing is key to Alzheimer's pathogenesis.
Area of Science:
- Neuroscience
- Neuropathology
- Biochemistry
Background:
- Alzheimer disease is characterized by amyloid plaques and tau tangles.
- Neurofilaments and tau protein are implicated in tangle formation.
- Previous studies questioned the presence of neurofilaments in tangles due to antibody cross-reactivity with tau protein.
Purpose of the Study:
- To re-evaluate the cross-reactivity of monoclonal antibodies (mAbs) with neurofilaments and tau protein.
- To determine the presence and contribution of neurofilaments in Alzheimer disease tangles and plaques.
- To investigate the role of abnormal protein processing in Alzheimer disease pathogenesis.
Main Methods:
- Immunocytochemical staining of Alzheimer disease tissue sections with various mAbs to phosphorylated and nonphosphorylated neurofilaments and tau protein.
- Immunoblot analysis to assess antibody cross-reactivity.
- Quantitative evaluation of staining intensities.
- Dephosphorylation of tissue sections prior to staining.
Main Results:
- Most mAbs to neurofilaments did not cross-react with tau protein in intact tissue sections.
- Neurofilaments were identified as constituents of Alzheimer disease tangles, with concentrations appearing 17-fold higher than tau protein.
- Abnormalities in neurofilament and tau protein processing were confirmed in Alzheimer disease.
- Cerebrovascular amyloid beta-protein processing is also abnormal in Alzheimer disease.
Conclusions:
- Neurofilaments are indeed constituents of Alzheimer disease tangles.
- The formation of plaques and tangles may be histological consequences rather than primary drivers of Alzheimer disease.
- Inhibition of processing for multiple proteins, including neurofilaments, tau, and amyloid beta-protein, is fundamental to Alzheimer disease pathogenesis.
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