Immunohistological and biochemical studies were initiated to determine whether or not neural membrane components were associated with degenerative changes characteristic of Alzheimer's disease (AD). Monoclonal antibody A2B5, developed against embryonic chick retinal cells and previously shown to react with neural surface gangliosides, was applied to formalin-fixed sections of control and AD brain tissue. Frontal cortex and hippocampus of AD cases exhibited high levels of A2B5 immunoreactivity within those neurons undergoing neurofibrillary degeneration. Neuritic processes associated with senile plaques were also highly reactive with the A2B5 antibody. The amount of gangliosides and their pattern after HPTLC were the same in control and AD cases. However, the unexpected observation was made that the A2B5 antibody reacted with human brain sulfatides in addition to the expected reactivity with minor gangliosides. The average level of sulfatides in AD brain was significantly higher than in normal controls. The data support the involvement of one or more membrane components with neurodegeneration in the Alzheimer brain.

Monoclonal antibodies to the A4 amyloid polypeptide were used in immunocytochemical saining of the Alzheimer disease prefrontal cortex. Analysis of the resulting staining patterns allowed us to evaluate the amounts and distribution of amyloid-protein deposits exclusive of other senile-plaque components. Previously unappreciated infrastructural details of amyloid in the Alzheimer disease brain became accessible through computer-enhanced imaging procedures. Four discrete morphologic classes of amyloid deposits were observed and classified as punctate, macular, ring, and ring-with-core configurations. Computer imaging indicated that all four classes of immunostained deposits contain internal gradients ofdensity. The classes were nonuniformly distributed with regard to size and location within cortical laminae. Our results support two separate but complementary hypotheses concerning the molecular neuropathology of Alzheimer disease in the prefrontal cortex. (i) Irrespective of cortical layer or morphology, density-gradient analyses suggest that amyloid deposits are elaborated through molecular and cellular events that may involve diffusion or coalescence ofthe A4 polypeptide.(it) The distribution and morphology of prefrontal cortical amyloid deposits may be dependent upon underlying laminarspecific structures of the neocortex.Senile plaques, found in abundance in the Alzheimer disease (AD) brain, contain a core with the A4 region of the amyloid precursor (1). Since the A4 cDNA domain cloned from AD brain mRNA has the same structure as that from nondemented brain (2), local cellular mechanisms may be significantly involved in the regulation of amyloid metabolism. In this regard no information is available on the relationship, if any, between discrete brain cytoarchitectural components and plaque size, morphology, or rate of amyloid accumulation. Indeed, the origin of the senile plaque has been a subject of speculation for at least six decades (3, 4).The present report addresses certain of these issues by focusing exclusively upon the A4 amyloid component of senile plaques as revealed by immunologic methods combined with computer-enhanced imaging, rather than traditional silver stains. With the newer approach, we observed unexpected morphologic diversity among amyloid deposits with respect to their size, morphology, internal composition, and laminar distribution. Specimens of prefrontal cortex immunostained for A4 amyloid were examined through a Leitz Laborlux 12 light microscope equipped with an MCI 65 televideo camera that interfaced with an AT&T PC6300 computer. The transmitted images of immunostained amyloid deposits were processed by Bioquant microdensitometry computer software equipped with pseudocolor optical density coding (R&M Biometrics, Nashville, TN). The computer, which perceives the range of optical density as a gray scale, was formatted to distinguish six levels of gray and to express each of these as a different color, as shown by the color bar in Fig. 3. The transmitted image was reconstructed...