Alzheimer's disease due to an intronic presenilin-1 (PSEN1 intron 4) mutation: a clinicopathological study

Janssen, JC, Hall, M, Fox, NC, Harvey, Richard J, Beck, J, Dickinson, A, Campbell, T, Collinge, J, Lantos, PL, Cipolotti, L, Stevens, JM and Rossor, MN 2000, Alzheimer's disease due to an intronic presenilin-1 (PSEN1 intron 4) mutation: a clinicopathological study, Brain, vol. 123, no. 5, pp. 894-907, doi: 10.1093/brain/123.5.894.

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Title Alzheimer's disease due to an intronic presenilin-1 (PSEN1 intron 4) mutation: a clinicopathological study
Author(s) Janssen, JC
Hall, M
Fox, NC
Harvey, Richard JORCID iD for Harvey, Richard J
Beck, J
Dickinson, A
Campbell, T
Collinge, J
Lantos, PL
Cipolotti, L
Stevens, JM
Rossor, MN
Journal name Brain
Volume number 123
Issue number 5
Start page 894
End page 907
Total pages 14
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2000-05
ISSN 0006-8950
Keyword(s) Alzheimer's disease
familial Alzheimer's disease
Apoliproprotein E
Summary We describe 21 affected individuals from a kindred with early-onset autosomal dominant familial Alzheimer's disease caused by an intronic presenilin-1 mutation (in intron 4). Mean age at onset of symptoms was 37.4 years [95% confidence interval (CI): 36.6-38.2 years], mean age at death was 44.7 years (95% CI: 43.1-46.3 years) and mean duration of illness was 7.3 years (95% CI: 5.9-8.7 years). Myoclonus and seizures were prominent features of this pedigree. In the four cases for whom neuropsychometric data were available, verbal memory impairment preceded visual memory deficits; naming was relatively preserved until late in the disease. One of these four cases underwent serial volumetric MRI scans demonstrating in vivo brain tissue loss of 3.9% (38.9 ml, annualized rate of atrophy: 1.7%) over 22 months of follow-up. The four individuals who had necropsies demonstrated the neuropathological hallmarks of Alzheimer's disease. Apolipoprotein E (APOE) status was assessed in five individuals: the case with the youngest age at onset at 33 years of age was found to be homozygous ε4/ε4, > 1 SD below the mean age of onset for those of known APOE genotype (36.4 ± 2.3 years, mean ± SD), and > 2 SDs below the mean age of onset for the pedigree as a whole (37.4 ± 1.7 years, mean ± SD). APOE genotype may therefore modulate age at onset in this pedigree.
Language eng
DOI 10.1093/brain/123.5.894
Indigenous content off
Field of Research 11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2000, Oxford University Press
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Document type: Journal Article
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School of Medicine
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