Accumulation of aspartic Acid(421)- and glutamic Acid(391)-Cleaved tau in neurofibrillary tangles correlates with progression in Alzheimer disease

作者：Basurto Islas Gustavo; Luna Munoz Jose; Guillozet Bongaarts Angela L; Binder Lester I; Mena Raul; Garcia Sierra Francisco^*

来源：Journal of Neuropathology and Experimental Neurology, 2008, 67(5): 470-483.

DOI：10.1097/nen.0b013e31817275c7

• Alzheimer disease
• ApoE epsilon 4 allele
• Braak staging
• neurofibrillary pathology
• tau proteolysis
• truncated tau

Truncations of tau protein at aspartic acid(421) (D(421)) and glutamic acid(391) (E(391)) residues are associated with neurofibrillary tangles (NFTs) in the brains of Alzheimer disease (AD) patients. Using inarnumohistochemistry with antibodies to D(421)- and E(391)-truncated tau (Tau-C3 and MN423, respectively), we correlated the presence of NFTs composed of these truncated tau proteins with clinical and neuropathologic parameters in 17 AD and 23 non-AD control brains. The densities of NFTs composed of D(421)- or E(391)-truncated tau correlated with clinical dementia index and Braak staging in AD. Glutamic acid(391) tau truncation was prominent in the entorhinal cortex, whereas D(421) truncation was prominent in the subiculum, suggesting that NFTs composed of either D(421)- or E(391)-truncated tau may be formed mutually exclusively in these areas. Both truncations were associated with the prevalence of the apolipoprotein E epsilon 4 allele. By double labeling, intact tau in NFTs was commonly associated with D(421)-deaved tau but not with E(391)-truncated tau; D(421)-cleaved tau was never associated with E(391)-truncated tau. These results indicate that tau is not randomly proteolyzed at different domains, and that proteolysis occurs sequentially from the C-terminus to inner regions of tau in AD progression. Identification of NFTs composed of tau at different stages of truncation may facilitate assessment of neurofibrillary pathology in AD.

• 出版日期2008-5
• 单位西北大学