TY - JOUR
T1 - Lewy body and Alzheimer pathology in a family with the amyloid-β precursor protein APP717 gene mutation
AU - Rosenberg, Carlyn K.
AU - Pericak-Vance, Margaret A.
AU - Saunders, Ann M.
AU - Gilbert, John R.
AU - Gaskell, Pete C.
AU - Hulette, Christine M.
N1 - Funding Information:
Acknowledgements We especially thank Dr. William K. Scott for thoughtful, insightful critical review of the manuscript. We extend gratitude to Dr. Allen D. Roses for the recruitment and assessment of genetics families. We gratefully acknowledge John Ervin for technical assistance, Anne Latham for preparation of the manuscript, and Steven Conlon and Susan Reeves for help with photography. We also wish to thank the autopsy nurses, Mari Szy-manski, RN, C and Nan Sinclaire, RN, C and all the family members involved in the decision to donate tissue of loved ones. We are particularly grateful to Dr. Samuel Orr, Dr. Henry Wilkinson, Dr. Robert Kinney, Dr. Eric Pittman and Dr. Patricia Konrad for performing autopsies. The Bryan Alzheimer’s Disease Research Cen- ter and the Kathleen Price Bryan Brain Bank are supported by NIH grant AG05128 and a research contract with Glaxo Wellcome Research and Development.
PY - 2000/8
Y1 - 2000/8
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - APP717 gene mutation
KW - Beta amyloid
KW - Dementia with Lewy bodies
KW - Parkinson's disease
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U2 - 10.1007/s004019900155
DO - 10.1007/s004019900155
M3 - Article
C2 - 10963361
AN - SCOPUS:0033938846
VL - 100
SP - 145
EP - 152
JO - Acta Neuropathologica
JF - Acta Neuropathologica
SN - 0001-6322
IS - 2
ER -