Acta Neuropathologica

, Volume 100, Issue 2, pp 145–152

Lewy body and Alzheimer pathology in a family with the amyloid-β precursor protein APP717 gene mutation

  • C. K. Rosenberg
  • M. A. Pericak-Vance
  • A. M. Saunders
  • J. R. Gilbert
  • P. C. Gaskell
  • C. M. Hulette
Regular Paper

DOI: 10.1007/s004019900155

Cite this article as:
Rosenberg, C., Pericak-Vance, M., Saunders, A. et al. Acta Neuropathol (2000) 100: 145. doi:10.1007/s004019900155

Abstract

Mutations in the amyloid precursor protein (APP) gene cause one form of early onset familial Alzheimer’s disease (AD). One such family has been studied genetically and neuropathologically and represents the basis of the present report. Four siblings with the APP717 Val to Ile mutation, aged 59, 65, 61 and 64 years, apolipoprotein E (APOE) genotyped 2,4 (first three) and 2,3 respectively, had severe AD, Braak stage VI with frequent neurofibrillary tangles in the primary visual cortex, Brodmann area 17. The first one also met McKeith criteria for the limbic stage of dementia with Lewy bodies but did not have substantia nigra Lewy bodies. The second two met McKeith criteria for the neocortical stage of dementia with Lewy bodies and both had substantia nigra Lewy bodies. The fourth had AD but no Lewy bodies. A cousin without the APP717 mutation who was APOE 3, 4, developed dementia at age 60 and died at age 75. She had severe cerebrovascular atherosclerosis, less severe AD, Braak stage V, with sparing of area 17. She also had Lewy bodies in the substantia nigra and in the cortex and met McKeith criteria for neocortical stage of dementia with Lewy bodies. Extrapyramidal features were present in all five. Lewy bodies have been described in 53% of reported autopsies on individuals with the APP717 Val to Ile mutation coincident with dementia and AD neuropathologic changes. These observations suggest an association between the chromosome 21 APP mutation and Lewy body formation, possibly mediated by other environmental or genetic factors.

Key words Alzheimer’s diseaseDementia with Lewy bodiesParkinson’s diseaseAPP717 gene mutationBeta amyloid

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • C. K. Rosenberg
    • 1
  • M. A. Pericak-Vance
    • 2
  • A. M. Saunders
    • 1
  • J. R. Gilbert
    • 2
  • P. C. Gaskell
    • 2
  • C. M. Hulette
    • 1
  1. 1.Bryan Alzheimer’s Disease Research Center, Division of Neurology, Department of Medicine, Box 2900, Duke University Medical Center, Durham, NC 27710, USAUS
  2. 2.Center for Human Genetics, Department of Medicine, Box 3445, Duke University Medical Center, Durham, NC 27710, USAUS
  3. 3.Department of Pathology, Box 2900, Duke University Medical Center, Durham, NC 27710, USA e-mail: hulet001@mc.duke.edu, Tel.: +1-919-6843801, Fax: +1-919-6846514US