Rw. Shin et al., ALZHEIMER-DISEASE A68 PROTEINS INJECTED INTO RAT-BRAIN INDUCE CODEPOSITS OF BETA-AMYLOID, UBIQUITIN, AND ALPHA-1-ANTICHYMOTRYPSIN, Proceedings of the National Academy of Sciences of the United Statesof America, 90(14), 1993, pp. 6825-6828
Aberrantly phosphorylated tau proteins (i.e., A68 or PHF-tau) and beta
-amyloid or A4 (betaA4) peptides are major components of pathologic le
sions in Alzheimer disease (AD). Although A68 and betaA4 colocalize in
AD neurofibrillary tangles (NFTs) and amyloid-rich senile plaques (SP
s), the mechanisms leading to the convergence of A68, betaA4, and othe
r proteins in the same AD lesions are unknown. To probe the biological
properties of A68 in vivo, and to assess interactions of A68 with end
ogenous proteins in the rodent brain, we injected A68, dephosphorylate
d A68 (DEP-A68), and normal adult human tau protein into the hippocamp
us and neocortex of rats. In marked contrast to DEP-A68 and tau, A68 r
esisted rapid proteolysis and induced codeposits of three rodent prote
ins-i.e., betaA4, ubiquitin, and alpha1-antichymotrypsin (ACT)-that ac
cumulate in AD NFTs and SPs together with A68. These findings suggest
that A68 may interact with betaA4, ubiquitin, and ACT in neuronal peri
karya as well as in the extracellular space after release of A68 from
degenerating neurons. The model system described here will facilitate
efforts to elucidate mechanisms leading to the convergence of A68, bet
aA4, ubiquitin, and ACT in hallmark lesions of AD.