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

被引：284

作者：

Crook, R

Verkkoniemi, A

Perez-Tur, J

Mehta, N

Baker, M

Houlden, H

Farrer, M

Hutton, M

Lincoln, S

Hardy, J

Gwinn, K

Somer, M

Paetau, A

Kalimo, H

Ylikoski, R

Pöyhönen, M

Kucera, S

Haltia, M

机构：

[1] Mayo Clin Jacksonville, Jacksonville, FL 32084 USA

[2] Univ Helsinki, Cent Hosp, Dept Clin Neurosci, FIN-00290 Helsinki, Finland

[3] Mayo Clin Scottsdale, Scottsdale, AZ 85259 USA

[4] Family Fed Finland, FIN-00101 Helsinki, Finland

[5] Univ Helsinki, Cent Hosp, Dept Pathol, FIN-00014 Helsinki, Finland

[6] Univ Helsinki, Haartman Inst, FIN-00014 Helsinki, Finland

[7] Univ Turku, Dept Pathol, FIN-20520 Turku, Finland

[8] Huddinge Hosp, Karolinska Inst, Div Geriatr Med, S-14186 Huddinge, Sweden

[9] Oulu Univ Hosp, Dept Clin Genet, FIN-90220 Oulu, Finland

[10] Univ Tampa, Dept Biol, Tampa, FL 33613 USA

来源：

NATURE MEDICINE | 1998年 / 4卷 / 04期

关键词：

D O I：

10.1038/nm0498-452

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 AP but lacked a congophilic dense core or marked plaque-related neuritic pathology. Molecular genetic analysis revealed that the disease was caused by a deletion of exon 9 (Delta 9) of the presenilin 1 (PSI) gene from the mRNA: unlike previous examples of the Delta 9 variant, the deletion was not caused by a splice acceptor site mutation.

引用

页码：452 / 455

页数：4

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