Differential sensitivity of the microtubule-associated protein, tau, in Alzheimer's disease tissue to formalin fixation

• Published in: The journal of histochemistry and cytochemistry Vol. 36; no. 9; pp. 1117 - 1121
• Main Authors: Pollock, NJ, Wood, JG
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA Histochemical Soc 01-09-1988; SAGE Publications; Histochemical Society
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Axons - analysis; Biological and medical sciences; Densitometry; Fixatives; Formaldehyde; Humans; Immunoassay; Immunohistochemistry; Lysine; Medical sciences; Microtubule-Associated Proteins - analysis; Nerve Tissue Proteins - analysis; Neurofibrils - analysis; Neurology; Periodic Acid; tau Proteins
• ISSN: 0022-1554; 1551-5044
• DOI: 10.1177/36.9.2841371

Immunohistochemistry of formalin-fixed human Alzheimer's disease (AD) tissue using an anti-tau antibody (Tau-1) reveals staining of neurofibrillary tangles (NFTs) and neuritic plaques (NPs), whereas normal axonal staining is less apparent. In this study, we used a combined biochemical and histochemical approach to assess effects of formalin on immunoreactivity of AD tau. Nitrocellulose blots were treated with fixative to mimic conditions used with tissue sections, a method that might be generally useful for assessing antigen sensitivity to different fixatives. A progressive decrease in Tau-1 immunoreactivity of the tau bands on a Western blot was observed with increasing times of formalin fixation. Phosphatase-digested blots demonstrated an increase in Tau-1 immunoreactivity compared to control blots. These results mimic the phosphatase-sensitive Tau-1 immunohistochemical staining of formalin-fixed AD tissue slices previously reported. Fixation of AD tissue with periodate-lysine-paraformaldehyde (PLP) preserves axonal tau antigenicity. Phosphatase digestion of PLP-fixed AD tissue enhances Tau-1 immunoreactivity of NFTs and NPs but does not alter axonal staining. These results indicate that axonal form(s) of tau are more sensitive to formalin fixation than pathology-associated tau. In addition, a modification of AD tau in pathological structures may protect it from the effects of formalin with regard to Tau-1 antigenicity.