Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation

S.G. Lindquist; J.E. Nielsen; J. Stokholm; M. Schwartz; M. Batbayli; M. Ballegaard; J. Erdal; K. Krabbe; G. Waldemar

Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation

S.G. Lindquist, J.E. Nielsen, J. Stokholm, M. Schwartz, M. Batbayli, M. Ballegaard, J. Erdal, K. Krabbe, G. Waldemar

Institut for Klinisk Medicin

16 Citationer (Scopus)

Abstract

BACKGROUND: Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features. METHODS AND RESULTS: We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer's disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense mutation, APP Thr714Ala (the Iranian mutation). CONCLUSIONS: The atypical clinical phenotype with long prodromal phase, autonomic failure and seizures in this new proband with the APP Thr714Ala mutation illustrates the clinical heterogeneity in families with identical pathogenic mutations
Udgivelsesdato: 2008/5/15

Originalsprog	Engelsk
Tidsskrift	Journal of the Neurological Sciences
Vol/bind	268
Udgave nummer	1-2
Sider (fra-til)	124-130
Antal sider	6
ISSN	0022-510X
Status	Udgivet - 2008

Citationsformater

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title = "Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation",

abstract = "BACKGROUND: Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features. METHODS AND RESULTS: We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer's disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense mutation, APP Thr714Ala (the Iranian mutation). CONCLUSIONS: The atypical clinical phenotype with long prodromal phase, autonomic failure and seizures in this new proband with the APP Thr714Ala mutation illustrates the clinical heterogeneity in families with identical pathogenic mutations Udgivelsesdato: 2008/5/15",

author = "S.G. Lindquist and J.E. Nielsen and J. Stokholm and M. Schwartz and M. Batbayli and M. Ballegaard and J. Erdal and K. Krabbe and G. Waldemar",

year = "2008",

language = "English",

volume = "268",

pages = "124--130",

journal = "Journal of the Neurological Sciences",

issn = "0022-510X",

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TY - JOUR

T1 - Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation

AU - Lindquist, S.G.

AU - Nielsen, J.E.

AU - Stokholm, J.

AU - Schwartz, M.

AU - Batbayli, M.

AU - Ballegaard, M.

AU - Erdal, J.

AU - Krabbe, K.

AU - Waldemar, G.

PY - 2008

Y1 - 2008

N2 - BACKGROUND: Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features. METHODS AND RESULTS: We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer's disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense mutation, APP Thr714Ala (the Iranian mutation). CONCLUSIONS: The atypical clinical phenotype with long prodromal phase, autonomic failure and seizures in this new proband with the APP Thr714Ala mutation illustrates the clinical heterogeneity in families with identical pathogenic mutations Udgivelsesdato: 2008/5/15

AB - BACKGROUND: Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features. METHODS AND RESULTS: We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer's disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense mutation, APP Thr714Ala (the Iranian mutation). CONCLUSIONS: The atypical clinical phenotype with long prodromal phase, autonomic failure and seizures in this new proband with the APP Thr714Ala mutation illustrates the clinical heterogeneity in families with identical pathogenic mutations Udgivelsesdato: 2008/5/15

M3 - Journal article

SN - 0022-510X

VL - 268

SP - 124

EP - 130

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

IS - 1-2

ER -