Early onset familial Alzheimer's disease: Mutation frequency in 31 families - PubMed (original) (raw)
Early onset familial Alzheimer's disease: Mutation frequency in 31 families
J C Janssen et al. Neurology. 2003.
Abstract
Background: Three causative genes have been identified for autosomal dominant AD.
Objective: To determine the proportion of patients with early onset AD with a positive family history accounted for by mutations in these genes.
Methods: A mutational analysis of the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes was performed in 31 probands with probable or definite AD from UK families with an age at onset (AAO) <61 years.
Results: The mean AAO was 46.9 years (median 45 years; range 33 to 60 years). The majority of patients (23 of 31; 74%) fulfilled recognized criteria for autosomal dominant inheritance. In 17 (55%) probands the authors identified eight novel PSEN1 sequence variants and eight recognized pathogenic mutations. In 4 (13%) probands the authors identified one novel APP sequence variant (H677R) and two recognized mutations. Thus in this series 21 of 31 (68%) probands were associated with a sequence variant in APP or PSEN1. Nine of the 11 (82%) probands with neuropathologically confirmed AD who additionally fulfilled recognized criteria for autosomal dominant inheritance were associated with a sequence variant in APP or PSEN1. The 10 patients in whom the authors were unable to identify a mutation in APP, PSEN1, or PSEN2 were older than the probands with sequence variants (55.4 vs 44.7 years: p = 0.001).
Conclusions: Sequence variants in APP and PSEN1 accounted for the majority of neuropathologically confirmed autosomal dominant early onset AD; no mutations in PSEN2 were detected. There may be a further genetic factor involved in the etiology of autosomal dominant early onset AD.
Similar articles
- Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia.
Arango D, Cruts M, Torres O, Backhovens H, Serrano ML, Villareal E, Montañes P, Matallana D, Cano C, Van Broeckhoven C, Jacquier M. Arango D, et al. Am J Med Genet. 2001 Oct 1;103(2):138-43. doi: 10.1002/1096-8628(20011001)103:2<138::aid-ajmg1529>3.0.co;2-8. Am J Med Genet. 2001. PMID: 11568920 - APP, PSEN1, and PSEN2 Mutations in Asian Patients with Early-Onset Alzheimer Disease.
Giau VV, Bagyinszky E, Youn YC, An SSA, Kim S. Giau VV, et al. Int J Mol Sci. 2019 Sep 25;20(19):4757. doi: 10.3390/ijms20194757. Int J Mol Sci. 2019. PMID: 31557888 Free PMC article. - Frequency of mutations in the presenilin and amyloid precursor protein genes in early-onset Alzheimer disease in Spain.
Lleó A, Blesa R, Queralt R, Ezquerra M, Molinuevo JL, Peña-Casanova J, Rojo A, Oliva R. Lleó A, et al. Arch Neurol. 2002 Nov;59(11):1759-63. doi: 10.1001/archneur.59.11.1759. Arch Neurol. 2002. PMID: 12433263 - [Genes in Alzheimer's disease].
Hoenicka J. Hoenicka J. Rev Neurol. 2006 Mar 1-15;42(5):302-5. Rev Neurol. 2006. PMID: 16538594 Review. Spanish. - [Genetic counseling and testing for families with Alzheimer's disease].
Kowalska A. Kowalska A. Neurol Neurochir Pol. 2004 Nov-Dec;38(6):495-501. Neurol Neurochir Pol. 2004. PMID: 15654674 Review. Polish.
Cited by
- Intergenerational epigenetic inheritance mediated by MYS-2/MOF in the pathogenesis of Alzheimer's disease.
Li Y, Bai H, Liu W, Zhou W, Gu H, Zhao P, Zhu M, Li Y, Yan X, Zhao N, Huang X. Li Y, et al. iScience. 2024 Jul 25;27(8):110588. doi: 10.1016/j.isci.2024.110588. eCollection 2024 Aug 16. iScience. 2024. PMID: 39220410 Free PMC article. - Conformational Changes and Unfolding of β-Amyloid Substrates in the Active Site of γ-Secretase.
Jakowiecki J, Orzeł U, Miszta P, Młynarczyk K, Filipek S. Jakowiecki J, et al. Int J Mol Sci. 2024 Feb 22;25(5):2564. doi: 10.3390/ijms25052564. Int J Mol Sci. 2024. PMID: 38473811 Free PMC article. - E674Q (Shanghai APP mutant), a novel amyloid precursor protein mutation, in familial late-onset Alzheimer's disease.
Zhang Y, Xie X, Chen B, Pan L, Li J, Wang W, Wang J, Tang R, Huang Q, Chen X, Ren R, Zhang Z, Fu W, Wang G. Zhang Y, et al. Genes Dis. 2023 Apr 10;11(2):1022-1034. doi: 10.1016/j.gendis.2023.02.051. eCollection 2024 Mar. Genes Dis. 2023. PMID: 37692508 Free PMC article. - WNT-β Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective.
Ramakrishna K, Nalla LV, Naresh D, Venkateswarlu K, Viswanadh MK, Nalluri BN, Chakravarthy G, Duguluri S, Singh P, Rai SN, Kumar A, Singh V, Singh SK. Ramakrishna K, et al. Diseases. 2023 Jun 25;11(3):89. doi: 10.3390/diseases11030089. Diseases. 2023. PMID: 37489441 Free PMC article. Review. - The Early-Onset Alzheimer's Disease Whole-Genome Sequencing Project: Study design and methodology.
Ray NR, Ayodele T, Jean-Francois M, Baez P, Fernandez V, Bradley J, Crane PK, Dalgard CL, Kuzma A, Nicaretta H, Sims R, Williams J, Cuccaro ML, Pericak-Vance MA, Mayeux R, Wang LS, Schellenberg GD, Cruchaga C, Beecham GW, Reitz C. Ray NR, et al. Alzheimers Dement. 2023 Sep;19(9):4187-4195. doi: 10.1002/alz.13370. Epub 2023 Jun 30. Alzheimers Dement. 2023. PMID: 37390458 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases