A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1 (original) (raw)

• Article
• Published: 01 April 1998
• Auli Verkkoniemi2,
• Jordi Perez-Tur1,
• Nitin Mehta1,
• Matt Baker1,
• Henry Houlden1,
• Matt Farrer1,
• Mike Hutton1,
• Sarah Lincoln1,
• John Hardy1,
• Katrina Gwinn3,
• Mirja Somer4,
• Anders Paetau5,
• Hannu Kalimo6,7,
• Raija Ylikoski2,
• Minna Pöyhönen8,
• Steve Kucera9 &
• …
• Matti Haltia5

Nature Medicine volume 4, pages 452–455 (1998)Cite this article

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Abstract

We describe a novel variant of Alzheimer's disease (AD) in a Finnish pedigree with 17 affected individuals of both sexes in three generations. The disease is characterized by progressive dementia which is, in most cases, preceded by spastic paraparesis. Neuropathological investigations revealed numerous, distinct, large, round and eosinophilic plaques as well as neurofibrillary tangles and amyloid angiopathy throughout the cerebral cortex. The predominant plaques resembled cotton wool balls and were immunoreactive for Aβ but lacked a con-gophilic dense core or marked plaque-related neuritic pathology. Molecular genetic analysis revealed that the disease was caused by a deletion of exon 9 (Δ9) of the presenilin 1 (PSI) gene from the mRNA: unlike previous examples of the Δ9 variant, the deletion was not caused by a splice acceptor site mutation.

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Authors and Affiliations

1. Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida, 32084, USA
   Richard Crook, Jordi Perez-Tur, Nitin Mehta, Matt Baker, Henry Houlden, Matt Farrer, Mike Hutton, Sarah Lincoln & John Hardy
2. Department of Clinical Neurosciences, Helsinki University Central Hospital, FIN-00290, Helsinki, Finland
   Auli Verkkoniemi & Raija Ylikoski
3. Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, Arizona, 85259, USA
   Katrina Gwinn
4. The Family Federation of Finland, P.O.Box 849, FIN-00101, Helsinki, Finland
   Mirja Somer
5. Department of Pathology, Helsinki University Central Hospital and Haartman Institute, University of Helsinki, FIN-00014, Helsinki, Finland
   Anders Paetau & Matti Haltia
6. Department of Pathology, University of Turku, FIN-20520, Turku, Finland
   Hannu Kalimo
7. Division of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, S-14186, Huddinge, Sweden
   Hannu Kalimo
8. Department of Clinical Genetics, Oulu University Hospital, FIN-90220, Oulu, Finland
   Minna Pöyhönen
9. Department of Biology, University of Tampa, Tampa, Florida, 33613, USA
   Steve Kucera

Authors

1. Richard Crook
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2. Auli Verkkoniemi
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3. Jordi Perez-Tur
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4. Nitin Mehta
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5. Matt Baker
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6. Henry Houlden
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7. Matt Farrer
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8. Mike Hutton
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9. Sarah Lincoln
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10. John Hardy
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11. Katrina Gwinn
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12. Mirja Somer
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13. Anders Paetau
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14. Hannu Kalimo
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15. Raija Ylikoski
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16. Minna Pöyhönen
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17. Steve Kucera
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18. Matti Haltia
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Crook, R., Verkkoniemi, A., Perez-Tur, J. et al. A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1.Nat Med 4, 452–455 (1998). https://doi.org/10.1038/nm0498-452

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• Received: 13 February 1998
• Accepted: 03 March 1998
• Issue Date: 01 April 1998
• DOI: https://doi.org/10.1038/nm0498-452

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