Abstract
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 β protein (Aß). We investigated brains of 131 subjects (ages 25–94 years, mean 72 years). Three distribution patterns of Aβ 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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abe K, Tanzi RE, Kogure K (1991) Selective induction of Kunitz-type protease inhibitor domain containing amyloid precursor protein mRNA after persistent focal ischemia in the rat cerebral cortex. Neurosci Lett 125: 172–174
Adams JH, Brierley JM, Connor RCR, Treip CS (1966) The effects of systemic hypotension upon the human brain. Clinical and neuropathological observations in 11 cases. Brain 89: 235–268
Braak H, Braak E (1991) Neuropathological staging of Alzbeimer-related changes. Acta Neuropathol 82: 239–259
Cochran E, Bacci B, Chen Y, Patton A, Gambetti P, Autilio-Gambetti L (1991) Amyloid precursor protein and ubiquitin immunoreactivity in dystrophic axons is not unique to Alzheimer's disease. Am J Pathol 139: 485–489
Davies L, Wolska B, Hilbich H, Multhaup G, Martins R, Simms G, Beyreuther K, Masters CL (1988) A4 amyloid protein deposition and the diagnosis of Alzheimer's disease: prevalence in aged brains determined by immunocytochemistry compared with conventional neuropathological techniques. Neurology 38: 1688–1693
Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE, Hennekens CH, Taylor JO (1989) Prevalence of Alzheimer's disease in a community population of older persons: higher than previously reported. JAMA 262: 2551–2556
Frackowiak RSJ, Pozzilli C, Legg NJ, Du Boulay GH, Marshall J, Lenzi GL, Jones T (1981) Regional cerebral oxygen supply and utilization in dementia. A climical and physiological study with oxygen-15 and positron tomography. Brain 104:753–778
Glenner GG, Wong CW (1984) Initial report on the purification and characterisation of a novel cerebro-vascular amyloid protein. Biochem Biophys Res Commun 120: 885–890
König G, Mönning U, Czech C, Prior R, Banati R, Schreiter-Gasser U, Bauer J, Masters CL, Beyreuther K (1992) Identification and differential expression of a novel alternative splice isoform of the β/A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells. J Biol Chem 267: 10804–10809
Lindenberg R (1955) Compression of brain arteries as pathogenetic factor for tissue necrosis and their areas of predilection. J Neuropathol Exp Neurol 14: 223–243
Mann DMA, Jones D, Prinja D, Purkiss MS (1990) The prevalence of amyloid (A4) protein deposits within the cerebral and cerebellar cortex in Down's syndrome and Alzheimer's disease. Acta Neuropathol 80: 318–327
Masters CL, Simms G, Weinmann NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer's disease and Down's syndrome. Proc Natl Acad Sci USA 82: 4245–4259
Meyer JE (1953) Über die Lokalisation frühkindlicher Hirnschäden in arteriellen Grenzgebieten. Arch Psychiatr Nervenkr 190: 238–241
Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, Belle G van, Berg L (1991) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). II. Standardization of the neuropathological assessment of Alzheimer's disease. Neurology 41: 479–86
Prohovnik I, Mayeux R, Sackeim HA, Smith G, Stern Y, Alderson PO (1988) Cerebral perfusion as a diagnostic marker of early Alzheimer's disease. Neurology 38: 931–937
Roberts GW, Gentleman SM, Lynch A, Graham DI (1991) ßA4-amyloid protein deposition in brain after head trauma. Lancet 338: 1422–1423
Solà C, García-Ladona FJ, Mengod G (1993) Increased levels of the Kunitz protease inhibitor-containing ßAPP mRNAs in rat brain following neurotoxic damage. Mol Brain Res 17: 41–52
Taraboulos A, Jendroska K, Serban D, Yang SL, DeArmond SJ, Prusiner SB (1992) Regional mapping of prion proteins in brain. Proc Natl Acad Sci USA 89: 7620–7624
Tomimoto H, Wakita H, Akiguchi I, Nakamura S, Kimura J (1994) Temporal profiles of accumulation of amyloid ß/A4 protein precursor in the gerbil after graded ischemic stress. J Cereb Blood Flow Metab 14: 565–573
Tomlinson BE, Blessed G, Roth M (1970) Observations on the brains of demented old people. J Neurol Sci 11: 205–242
Van Nostrand WE, Wagner SL, Suzuki M, Choi BH, Farrow JS, Geddes JW, Cotman CW, Cunningham DD (1989) Protease nexin-II, a potent anti-chymotrypsin, shows identity to amyloid b-protein precursor. Nature 341: 546–549
Zapata JE, Cervós-Navarro J (1969) Der vasculäre Faktor bei der Genese der akuten nekrotisierenden Encephalitis. Dtsch Z Nervenheilkd 195: 199–218
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jendroska, K., Poewe, W., Pluess, J. et al. Ischemic stress induces deposition of amyloid β immunoreactivity in human brain. Acta Neuropathol 90, 461–466 (1995). https://doi.org/10.1007/BF00294806
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00294806