THE PROGRESSION OF BETA-AMYLOID DEPOSITION IN THE FRONTAL-CORTEX OF THE AGED CANINE

Brains from 41 aged canines (greater than or equal to 10 years of age) were examined immunohistochemically to characterize the laminar distr ibution and age-related progression of beta-amyloid (A beta) in fronta l cortex. We classified the AP patterns into four distinct types. Type I was characterized by small, faint deposits of A beta in deep cortic al layers. Type II consisted of diffuse deposits of A beta mainly in l ayers V and VI. Type III had both dense plaques in superficial layers, and diffuse deposits in deep layers. Finally, Type IV had solely dens e plaques throughout all layers of cortex. We compared the A beta dist ribution pattern between the Old canines (10-15 years, n = 22) and the Very Old canines (> 15 years, n = 19). The Old group primarily had ne gative staining, or Type I and Type II patterns of amyloid deposition (73%). Conversely, the Very Old group had predominantly Types II, III and IV deposits (89.5%), a difference that was significant (P < 0.05). We suggest that A beta deposition in canine frontal cortex is a progr essive age-related process beginning with diffuse deposits in the deep cortical layers followed by the development of deposits in outer laye rs. In support of this hypothesis, the deeper layer diffuse plaques in the Very Old group of dogs also contain the largest proportion of bet a-amyloid with an isomerized aspartic acid residue at position 7, indi cating that these deposits had been present for some time. We also obs erved fiber-like A beta immunoreactivity within regions of diffuse A b eta deposits. These fibers appeared to be degenerating neurites, which were negative for hyperphosphorylated tau. Therefore, these fibers ma y represent a very early form of neuritic change that precede tau hype rphosphorylation or develop by an alternative pathway. (C) 1997 Elsevi er Science B.V.