DISTRIBUTION OF NEURONAL GROWTH-PROMOTING FACTORS AND CYTOSKELETAL PROTEINS IN ALTERED NEURITES IN ALZHEIMERS-DISEASE AND NONDEMENTED ELDERLY

In the present immunohistochemical study, we investigated the characte ristics of altered neurites in the frontal cortex of 10 Alzheimer's di sease (AD) brains and 15 age-matched non-demented control brains. In b oth AD and control cases, the altered neurites in coronas of the class ical plaques (CP) were frequently immunostained by antibodies to growt h-promoting factors, N and C termini of amyloid precursor protein (APP ), GAP43, collagen IV, laminin and the integrin receptor VLA6. The alt ered neu rites in CP coronas in AD but not in controls were also immun ostained by antibodies against normally and abnormally phosphorylated tau. Immunolabeling for microtubule-associated protein 2 was not found in CP from either group. Extensive neuropil threads (NT) and many neu rofibrillary tangles (NFT), immunostained with tau and Alz50 antibodie s, were present in AD neocortex but not seen in control cases. NT and NFT could not be stained by antibodies to the N termini of APP, GAP43, collagen IV, laminin and VLA6. Our findings indicate that in AD cases altered neurites in CP are undergoing both an aberrant sprouting proc ess and a degenerating process. These altered neurites are probably of axon origin. NT and NFT may represent destructive changes. The presen ce of amyloid plaques, but absence of tau-related cytoskeletal patholo gy, in non-demented cases suggests that beta/A4 peptide is necessary b ut not sufficient to induce neurofibrillary pathology.