DIFFUSE, LAKE-LIKE AMYLOID-BETA DEPOSITS IN THE PARVOPYRAMIDAL LAYER OF THE PRESUBICULUM IN ALZHEIMER-DISEASE

A characteristic feature of the parvopyramidal layer of the presubicul um of 6 individuals with Alzheimer disease (AD) was the presence of la rge, evenly distributed amyloid-beta (A beta) deposits, which in the e nd stage of the disease occupy 80.9 +/- 12.2 % of the parvopyramidal l ayer. The strong reaction of AP deposits with antibodies 4G8 (17-24 am ino acids, aa), 6E10 (1-17 aa), and R165 (32-42 aa), and their weak re action with antibody R162 (32-40 aa) indicate that potentially highly fibrillogenic A beta I-42 is a major constituent of presubicular amylo id. However, A beta deposits in the presubiculum are thioflavin-S- and Congo red-negative-and thus, nonfibrillar-even after 11 to 19 years o f AD. The unique properties of presubicular amyloid appear to be relat ed to their origin; amyloid-associated proteins such as apolipoprotein s E, and AI, alpha(1)-antichymotrypsin, and heparan sulfate proteoglyc an, which are promoters of fibrillization or stabilizers of A beta in neuritic plaques, are absent; activated astrocytes, which are the sour ce of these proteins, are also absent. The unchanged number and distri bution and the resting appearance of microglial cells revealed with RC A-I histochemistry suggest that they do not respond to diffuse A beta deposits. The source of nonfibrillar presubicular A beta is probably l ocal neurons or neuronal projections to the parvocellular layer of the presubiculum. Neuronal, lake-like A beta deposition appears to be cha racteristic of AD pathology. The presubiculum is most likely the model brain structure for the study of amyloid of exclusively neuronal orig in. The parvopyramidal layer of the presubiculum reveals only a small population of the neurons (2.5 +/- 2%) affected by neurofibrillary pat hology.