ISCHEMIC STRESS INDUCES DEPOSITION OF AMYLOID-BETA IMMUNOREACTIVITY IN HUMAN BRAIN

The histoblot immunostaining technique for locating and characterizing amyloidogenic proteins was used to obtain information about the relationship of cerebral ischemia/hypoxia to the accumulation of amyloid beta protein (A beta). We investigated brains of 131 subjects (ages 25-94 years, mean 72 years). Three distribution patterns of A beta immunoreactivity were identified: (1) colocalization with diffuse and neuritic plaques of Alzheimer's disease (AD) and aging; (2) diffuse punctate deposits in the cerebral cortex in association with small vessel cerebral vascular disease and (3) cerebral cortical accumulation localized to arterial boundary zones and other regions susceptible to ischemic/hypoxic injury designated ''stress-induced deposits'' (SID). SID were not identified in tissue sections by immunohistochemical, Congo red or Bielschowsky silver techniques; no histological abnormalities were present in adjacent formalin-fixed tissue sections. SID occurred in subjects with histories of cerebral ischemia, and severe orthostatic hypotension. There was also an association with aging in general and with the incidence of neuritic plaques specifically. These latter findings are consistent with the hypothesis that brain ischemia/hypoxia plays a role in the pathogenesis of AD.