Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease.

BIOCHEMICAL ANALYSES OF ALZHEIMER BRAIN LESIONS LEAD TO THE IDENTIFICATION OF A� AND ITS PRECURSOR . . . . . . . . . . . . . . . . . . . 374 The Histopathology of Alzheimer's Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374 Characterization of A � and �pp . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376 AL TERNA TIVE PROTEOLYTIC PROCESSING OF �PP AND THE GENERATION OF A� 378 GENETIC EVIDENCE IMPLICATES A� IN THE PATHOGENESIS OF FAMILIAL ALZHEIMER'S DISEASE 380 SEVERAL POTENTIAL FUNCTIONS HAVE BEEN ASCRIBED TO �PP . . . . . . . . . 383 CELL BIOLOGICAL STUDIES OF THE TRAFFICKING AND SECRETORY PROCESSING OF �PP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385 �pp Traf icking in Polarized Epithelial Cells ........ . 389 SECRETORY PROCESSING OF �PP IS UNDER COMPLEX REGULATION BY FIRST MESSENGERS . . . . . ......... 391 UNDERSTANDING THE ROLE OF J3PP PROCESSING IN THE PATHOGENETIC CASCADE OF AD .. . .. . 393 CONCLUSION ... . ..... . 397