Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene

Rogaev, E. I.; Sherrington, R.; Rogaeva, E. A.; Levesque, G.; Ikeda, M.; Liang, Y.; Chi, H.; Lin, C.; Holman, K.; Tsuda, T.; Mar, L.; Sorbi, S.; Nacmias, B.; Piacentini, S.; Amaducci, L.; Chumakov, I.; Cohen, D.; Lannfelt, L.; Fraser, P. E.; Rommens, J. M.; George-Hyslop, P. H. St

doi:10.1038/376775a0

Cited by 2,052Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene

Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C. +13 more·1995·Nature

DOI 10.1038/376775a0

Open this paper in CoChat — free account

Abstract

We report the cloning of a novel gene (E5-1) encoded on chromosome 1 which has substantial nucleotide and amino-acid sequence similarity to the S182 gene on chromosome 14q24.3. Mutations, including three new missense mutations in the S182 gene, are associated with the AD3 subtype of early-onset familial Alzheimer's disease (AD). Both the E5-1 and the S182 proteins are predicted to be integral membrane proteins with seven membrane-spanning domains, and a large exposed loop between the sixth and seventh transmembrane domains. Analysis of the nucleotide sequence of the open reading frame (ORF) of the E5-1 gene led to the discovery of two missense substitutions at conserved amino-acid residues in affected members of pedigrees with a form of familial AD that has a later age of onset than the AD3 subtype (50-70 years versus 30-60 years for AD3). These observations imply that the E5-1 gene on chromosome 1 and the S182 gene on chromosome 14q24.3 are members of a family of genes (presenilins) with related functions, and indicates that mutations in conserved residues of E5-1 could also play a role in the genesis of AD. Our results also indicate that still other AD susceptibility genes exist.

Integrity signals

Registry

Crossref · 10.1038/376775a0

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The amyloid cascade hypothesis is strongly supported by neuropathological and human genetic evidence.
“The amyloid cascade hypothesis of Alzheimer disease (AD), which proposes that deposition of the amyloid-β (Aβ) peptide in the brain is a central event in disease pathology (Figure 1), is strongly supported by neuropathological and human genetic evidence”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [4]

Basic local alignment search tool
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669 · see citing works
A simple method for displaying the hydropathic character of a protein
Kyte, J., & Doolittle, R. F. (1982) · Journal of Molecular Biology · doi:10.1016/0022-2836(82)90515-0 · Cited by 22,694 · see citing works
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051 · see citing works
Self-citation
Cloned Glutamate Receptors
Hollmann, M., & Heinemann, S. F. (1994) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.17.030194.000335 · Cited by 4,011 · see citing works
Genetic Linkage Evidence for a Familial Alzheimer's Disease Locus on Chromosome 14
Schellenberg, G. D., Bird, T. D., Wijsman, E. M., Orr, H. T., Anderson, L., Nemens, E. J., White, J. A., Bonnycastle, L. L., Weber, J. L., Alonso, M. E., et al. (1992) · Science · doi:10.1126/science.1411576 · Cited by 945 · see citing works
Familial alzheimer's disease in american descendants of the volga germans: Probable genetic founder effect
Bird, T. D., Lampe, T. H., Nemens, E. J., Miner, G. W., Sumi, S. M., & Schellenberg, G. D. (1988) · Annals of Neurology · doi:10.1002/ana.410230106 · Cited by 147 · see citing works
Studies in aging of the brain
Cook-Deegan, R. M., Ward, B. E., & Austin, J. H. (1979) · Neurology · doi:10.1212/wnl.29.10.1402 · Cited by 117 · see citing works
No linkage to chromosome 14 in Swedish Alzheimer's disease families
Lannfelt, L., Lilius, L., Appelgren, H., et al. (1993) · Nature Genetics · doi:10.1038/ng0793-218 · Cited by 20 · see citing works
Self-citation

Flagged first, then by citations

Sorted by citations

Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium, Whitehead Institute for Biomedical Research, C. F. G. R., Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., et al. (2001) · Nature · doi:10.1038/35057062 · Cited by 24,216 · see citing works
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240 · see citing works
TREM2 Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
Self-citation
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708 · see citing works
Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
Self-citation
Oxidative stress hypothesis in Alzheimer’s disease
Markesbery, W. R. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00629-6 · Cited by 2,383 · see citing works
The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics
Karran, E., Mercken, M., & Strooper, B. D. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3505 · Cited by 2,188 · see citing works
The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952 · see citing works
Self-citation
Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease
Naj, A. C., Jun, G., Beecham, G. W., Wang, L.-S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., et al. (2011) · Nature Genetics · doi:10.1038/ng.801 · Cited by 1,901 · see citing works
Self-citation
Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase
Jankowsky, J. L., Fadale, D. J., Anderson, J., Xu, G. M., Gonzales, V., Jenkins, N. A., Copeland, N. G., Lee, M. K., Younkin, L. H., Wagner, S. L., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh019 · Cited by 1,575 · see citing works
Familial Alzheimer's Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In Vivo
Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., Prada, C.-M., Kim, G., Seekins, S., Yager, D., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80230-5 · Cited by 1,478 · see citing works
Amyloid, the presenilins and Alzheimer’s disease
Hardy, J. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)01030-2 · Cited by 1,370 · see citing works
Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice
Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-wood, K., Lee, M., Seubert, P., Davis, A., et al. (1997) · Nature Medicine · doi:10.1038/nm0197-67 · Cited by 1,271 · see citing works
Self-citation
Deciphering the Molecular Basis of Memory Failure in Alzheimer's Disease
Walsh, D. M., & Selkoe, D. J. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.010 · Cited by 1,207 · see citing works
The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease
Rogaeva, E., Meng, Y., Lee, J. H., Gu, Y., Kawarai, T., Zou, F., Katayama, T., Baldwin, C. T., Cheng, R., Hasegawa, H., et al. (2007) · Nature Genetics · doi:10.1038/ng1943 · Cited by 1,167 · see citing works
Self-citation
Review Article: Genetics of Alzheimer Disease
Bekris, L. M., Yu, C.-E., Bird, T. D., & Tsuang, D. W. (2010) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988710383571 · Cited by 1,029 · see citing works
Accelerated Amyloid Deposition in the Brains of Transgenic Mice Coexpressing Mutant Presenilin 1 and Amyloid Precursor Proteins
Borchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., Copeland, N. G., Price, D. L., & Sisodia, S. S. (1997) · Neuron · doi:10.1016/s0896-6273(00)80974-5 · Cited by 1,023 · see citing works
Amyloid β-based therapy for Alzheimer’s disease: Challenges, successes and future
Zhang, Y., Chen, H., Li, R., Sterling, K., & Song, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01484-7 · Cited by 988 · see citing works
Microglia in Alzheimer's disease
Sarlus, H., & Heneka, M. T. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90606 · Cited by 911 · see citing works
The amyloid hypothesis for Alzheimer’s disease: A critical reappraisal
Hardy, J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06181.x · Cited by 814 · see citing works
The genetics of Alzheimer disease
Tanzi, R. E. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006296 · Cited by 727 · see citing works
The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics
Karran, E., & De Strooper, B. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00391-w · Cited by 742 · see citing works
Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses
Bertram, L., & Tanzi, R. E. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2494 · Cited by 747 · see citing works
TREM2 — a key player in microglial biology and Alzheimer disease
Ulland, T. K., & Colonna, M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0072-1 · Cited by 735 · see citing works
History and progress of hypotheses and clinical trials for Alzheimer’s disease
Liu, P.-P., Xie, Y., Meng, X.-Y., & Kang, J.-S. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0063-8 · Cited by 723 · see citing works
Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs
Forman, M. S., Trojanowski, J. Q., & Lee, V. M.-Y. (2004) · Nature Medicine · doi:10.1038/nm1113 · Cited by 715 · see citing works
The genetic epidemiology of neurodegenerative disease
Bertram, L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24761 · Cited by 680 · see citing works
The Aging Brain
Yankner, B. A., Lu, T., & Loerch, P. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.2.010506.092044 · Cited by 677 · see citing works
Late onset Alzheimer’s disease genetics implicates microglial pathways in disease risk
Efthymiou, A. G., & Goate, A. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0184-x · Cited by 562 · see citing works
Molecular genetics of early-onset Alzheimer’s disease revisited
Cacace, R., Sleegers, K., & Van Broeckhoven, C. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.01.012 · Cited by 617 · see citing works
APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases
Lanoiselée, H.-M., Nicolas, G., Wallon, D., Rovelet-Lecrux, A., Lacour, M., Rousseau, S., Richard, A.-C., Pasquier, F., Rollin-Sillaire, A., Martinaud, O., et al. (2017) · PLOS Medicine · doi:10.1371/journal.pmed.1002270 · Cited by 616 · see citing works
Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy
Muzio, L., Viotti, A., & Martino, G. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.742065 · Cited by 581 · see citing works
Self-Organizing 3D Human Neural Tissue Derived from Induced Pluripotent Stem Cells Recapitulate Alzheimer’s Disease Phenotypes
Raja, W. K., Mungenast, A. E., Lin, Y.-T., Ko, T., Abdurrob, F., Seo, J., & Tsai, L.-H. (2016) · PLOS ONE · doi:10.1371/journal.pone.0161969 · Cited by 569 · see citing works
Linking Aβ and Tau in Late-Onset Alzheimer's Disease: A Dual Pathway Hypothesis
Small, S. A., & Duff, K. (2008) · Neuron · doi:10.1016/j.neuron.2008.11.007 · Cited by 546 · see citing works
Genome-wide Association Analysis Reveals Putative Alzheimer's Disease Susceptibility Loci in Addition to APOE
Bertram, L., Lange, C., Mullin, K., Parkinson, M., Hsiao, M., Hogan, M. F., Schjeide, B. M. M., Hooli, B., DiVito, J., Ionita, I., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.10.008 · Cited by 511 · see citing works
γ-Secretase, notch, Aβ and alzheimer's disease: Where do the presenilins fit in?
Sisodia, S. S., & St George-Hyslop, P. H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn785 · Cited by 512 · see citing works
REVIEW: Curcumin and Alzheimer’s disease
Hamaguchi, T., Ono, K., & Yamada, M. (2010) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00147.x · Cited by 450 · see citing works
Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes
Jun, G. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.201 · Cited by 422 · see citing works
Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors
Goldman, J. S., Hahn, S. E., Catania, J. W., Larusse-Eckert, S., Butson, M. B., Rumbaugh, M., Strecker, M. N., Roberts, J. S., Burke, W., Mayeux, R., et al. (2011) · Genetics in Medicine · doi:10.1097/gim.0b013e31821d69b8 · Cited by 393 · see citing works
Emerging diagnostics and therapeutics for Alzheimer disease
Self, W. K., & Holtzman, D. M. (2023) · Nature Medicine · doi:10.1038/s41591-023-02505-2 · Cited by 381 · see citing works
Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations
Song, W., Nadeau, P., Yuan, M., Yang, X., Shen, J., & Yankner, B. A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.12.6959 · Cited by 362 · see citing works
Glycosylation of microtubule–associated protein tau: An abnormal posttranslational modification in Alzheimer's disease
Wang, J.-Z., Grundke-Iqbal, I., & Iqbal, K. (1996) · Nature Medicine · doi:10.1038/nm0896-871 · Cited by 360 · see citing works
Clinical Features of Early-Onset Alzheimer Disease in a Large Kindred With an E280A Presenilin-1 Mutation
Lopera, F. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03540340027028 · Cited by 351 · see citing works
Genetics of dementia
Loy, C. T., Schofield, P. R., Turner, A. M., & Kwok, J. B. (2014) · The Lancet · doi:10.1016/s0140-6736(13)60630-3 · Cited by 342 · see citing works
Age at Onset in Two Common Neurodegenerative Diseases Is Genetically Controlled
Li, Y.-J., Scott, W. K., Hedges, D. J., Zhang, F., Gaskell, P. C., Nance, M. A., Watts, R. L., Hubble, J. P., Koller, W. C., Pahwa, R., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/339815 · Cited by 312 · see citing works
Use of Caenorhabditis elegans as a model to study Alzheimerâ€™s disease and other neurodegenerative diseases
Alexander, A. G., Marfil, V., & Li, C. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00279 · Cited by 310 · see citing works
The Ratio of Monomeric to Aggregated Forms of Aβ40 and Aβ42 Is an Important Determinant of Amyloid-β Aggregation, Fibrillogenesis, and Toxicity
Jan, A., Gokce, O., Luthi-Carter, R., & Lashuel, H. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803159200 · Cited by 291 · see citing works
Genetics of familial and sporadic Alzheimer s disease
Piaceri, I. (2013) · Frontiers in Bioscience · doi:10.2741/e605 · Cited by 256 · see citing works
Untangling Genetic Risk for Alzheimer’s Disease
Pimenova, A. A., Raj, T., & Goate, A. M. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.05.014 · Cited by 223 · see citing works
Amyloid precursor protein (APP) and the biology of proteolytic processing: relevance to Alzheimer’s disease
Ling, Y., Morgan, K., & Kalsheker, N. (2003) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(03)00133-x · Cited by 224 · see citing works
Oxidant/Antioxidant Imbalance in Alzheimer’s Disease: Therapeutic and Diagnostic Prospects
Wojsiat, J., Zoltowska, K. M., Laskowska-Kaszub, K., & Wojda, U. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/6435861 · Cited by 221 · see citing works
Neurotherapeutic applications of nanoparticles in Alzheimer’s disease
Sahni, J. K., Doggui, S., Ali, J., Baboota, S., Dao, L., & Ramassamy, C. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.033 · Cited by 219 · see citing works
Gene–environment interactions in Alzheimer disease: the emerging role of epigenetics
Migliore, L., & Coppedè, F. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00714-w · Cited by 217 · see citing works
Mouse Models of Alzheimer’s Disease
Yokoyama, M., Kobayashi, H., Tatsumi, L., & Tomita, T. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.912995 · Cited by 213 · see citing works
Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer’s Disease Genetics
Podleśny-Drabiniok, A., Marcora, E., & Goate, A. M. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.002 · Cited by 211 · see citing works
Towards a Better Understanding of GABAergic Remodeling in Alzheimer’s Disease
Govindpani, K., Calvo-Flores Guzmán, B., Vinnakota, C., Waldvogel, H., Faull, R., & Kwakowsky, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081813 · Cited by 208 · see citing works
Activation of Ras-ERK Signaling and GSK-3 by Amyloid Precursor Protein and Amyloid Beta Facilitates Neurodegeneration in Alzheimer’s Disease
Kirouac, L., Rajic, A. J., Cribbs, D. H., & Padmanabhan, J. (2017) · eneuro · doi:10.1523/eneuro.0149-16.2017 · Cited by 207 · see citing works
Structural basis of γ-secretase inhibition and modulation by small molecule drugs
Yang, G., Zhou, R., Guo, X., Yan, C., Lei, J., & Shi, Y. (2021) · Cell · doi:10.1016/j.cell.2020.11.049 · Cited by 189 · see citing works
TUDCA, a Bile Acid, Attenuates Amyloid Precursor Protein Processing and Amyloid-β Deposition in APP/PS1 Mice
Nunes, A. F., Amaral, J. D., Lo, A. C., Fonseca, M. B., Viana, R. J. S., Callaerts-Vegh, Z., D’Hooge, R., & Rodrigues, C. M. P. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8256-y · Cited by 192 · see citing works
Neurovascular Dysfunction in Vascular Dementia, Alzheimer's and Atherosclerosis
Shabir, O., Berwick, J., & Francis, S. E. (2018) · BMC Neuroscience · doi:10.1186/s12868-018-0465-5 · Cited by 191 · see citing works
Amyloid β protein (Aβ) deposition in chromosome 14–linked Alzheimer's disease: Predominance of Aβ42(43)
Mann, D. M. A., Iwatsubo, T., Cairns, N. J., Lantos, P. L., Nochlin, D., Sumi, S. M., Bird, T. D., Poorkaj, P., Hardy, J., Hutton, M., et al. (1996) · Annals of Neurology · doi:10.1002/ana.410400205 · Cited by 184 · see citing works
TREM2 in CNS homeostasis and neurodegenerative disease
Painter, M. M., Atagi, Y., Liu, C.-C., Rademakers, R., Xu, H., Fryer, J. D., & Bu, G. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0040-9 · Cited by 169 · see citing works
Molecular Genetics of Late‐Onset Alzheimer's Disease
Kamboh, M. I. (2004) · Annals of Human Genetics · doi:10.1046/j.1529-8817.2004.00110.x · Cited by 170 · see citing works
Light and Electron Microscopic Localization of Presenilin-1 in Primate Brain
Lah, J. J., Heilman, C. J., Nash, N. R., Rees, H. D., Yi, H., Counts, S. E., & Levey, A. I. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-06-01971.1997 · Cited by 168 · see citing works
The presenilin genes: a new gene family involved in Alzheimer disease pathology
Cruts, M., Hendriks, L., & Van Broeckhoven, C. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.supplement_1.1449 · Cited by 163 · see citing works
Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans
Logue, M. W., Schu, M., Vardarajan, B. N., Farrell, J., Bennett, D. A., Buxbaum, J. D., Byrd, G. S., Ertekin‐Taner, N., Evans, D., Foroud, T., et al. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.06.010 · Cited by 136 · see citing works
Protein Folding in the Endoplasmic Reticulum and the Unfolded Protein Response
Zhang, K., & Kaufman, R. J. (2005) · Handbook of Experimental Pharmacology · doi:10.1007/3-540-29717-0_3 · Cited by 152 · see citing works
Brahmi (Bacopa monnieri): An ayurvedic herb against the Alzheimer's disease
Dubey, T., & Chinnathambi, S. (2019) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2019.108153 · Cited by 151 · see citing works
Metals and Neuronal Metal Binding Proteins Implicated in Alzheimer’s Disease
Cristóvão, J. S., Santos, R., & Gomes, C. M. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/9812178 · Cited by 146 · see citing works
Making the final cut: Pathogenic amyloid-β peptide generation by γ-secretase
Steiner, H., Fukumori, A., Tagami, S., & Okochi, M. (2018) · Cell Stress · doi:10.15698/cst2018.11.162 · Cited by 133 · see citing works
Biochemistry and Molecular Biology of Amyloid β‐Protein and the Mechanism of Alzheimer's Disease
(2008) · Handbook of Clinical Neurology · doi:10.1016/s0072-9752(07)01223-7 · Cited by 137 · see citing works
Reduced Reelin Expression Accelerates Amyloid- Plaque Formation and Tau Pathology in Transgenic Alzheimer's Disease Mice
Kocherhans, S., Madhusudan, A., Doehner, J., Breu, K. S., Nitsch, R. M., Fritschy, J.-M., & Knuesel, I. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0418-10.2010 · Cited by 132 · see citing works
Parenchymal and vascular Aβ‐deposition and its effects on the degeneration of neurons and cognition in Alzheimer's disease
Thal, D. R., Griffin, W. S. T., & Braak, H. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00411.x · Cited by 134 · see citing works
Animal models of Alzheimer disease: historical pitfalls and a path forward
Cavanaugh, S. E. (2014) · ALTEX · doi:10.14573/altex.1310071 · Cited by 132 · see citing works
The pursuit of susceptibility genes for Alzheimer's disease: progress and prospects
Sleegers, K., Lambert, J.-C., Bertram, L., Cruts, M., Amouyel, P., & Van Broeckhoven, C. (2010) · Trends in Genetics · doi:10.1016/j.tig.2009.12.004 · Cited by 129 · see citing works
Genetic architecture of Alzheimer's disease
Neuner, S. M., TCW, J., & Goate, A. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104976 · Cited by 126 · see citing works
“The first disease-causative mutations in these genes were identified in 1995 [42, 43], although it”
Background
Intraneuronal APP/Aβ Trafficking and Plaque Formation in β‐Amyloid Precursor Protein and Presenilin‐1 Transgenic Mice
Wirths, O., Multhaup, G., Czech, C., Feldmann, N., Blanchard, V., Tremp, G., Beyreuther, K., Pradier, L., & Bayer, T. A. (2002) · Brain Pathology · doi:10.1111/j.1750-3639.2002.tb00442.x · Cited by 125 · see citing works
Circulating Biomarkers of Cognitive Decline and Dementia
Solfrizzi, V., D'Introno, A., Colacicco, A. M., Capurso, C., Todarello, O., Pellicani, V., Capurso, S. A., Pietrarossa, G., Santamato, V., Capurso, A., et al. (2006) · Clinica Chimica Acta · doi:10.1016/j.cca.2005.06.015 · Cited by 120 · see citing works
Amyloid‐β protein (Aβ) Glu11 is the major β‐secretase site of β‐site amyloid‐β precursor protein‐cleaving enzyme 1(BACE1), and shifting the cleavage site to Aβ Asp1 contributes to Alzheimer pathogenesis
Deng, Y., Wang, Z., Wang, R., Zhang, X., Zhang, S., Wu, Y., Staufenbiel, M., Cai, F., & Song, W. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12235 · Cited by 108 · see citing works
Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease
Beck, J. A. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh134 · Cited by 102 · see citing works
Increased Aβ42(43) from cell lines expressing presenilin 1 mutations
Mehta, N. D., Refolo, L. M., Eckman, C., Sanders, S., Yager, D., Perez‐Tur, J., Younkin, S., Duff, K., Hardy, J., & Hutton, M. (1998) · Annals of Neurology · doi:10.1002/ana.410430217 · Cited by 101 · see citing works
Presenilins and Alzheimer's disease
Kim, T.-W., & Tanzi, R. E. (1997) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(97)80089-x · Cited by 97 · see citing works
Genetics of age-related macular degeneration: current concepts, future directions
DeAngelis, M. M., Silveira, A. C., Carr, E. A., & Kim, I. K. (2011) · Seminars in Ophthalmology · doi:10.3109/08820538.2011.577129 · Cited by 94 · see citing works
Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases
Knuesel, I. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.04.002 · Cited by 89 · see citing works
The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics
Pritchard, S. M., Dolan, P. J., Vitkus, A., & Johnson, G. V. W. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01273.x · Cited by 89 · see citing works
Shifting paradigms: The central role of microglia in Alzheimer’s disease
Schwabe, T., Srinivasan, K., & Rhinn, H. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104962 · Cited by 84 · see citing works
APOE and other loci affect age‐at‐onset in Alzheimer's disease families with PS2 mutation
Wijsman, E. M., Daw, E. W., Yu, X., Steinbart, E. J., Nochlin, D., Bird, T. D., & Schellenberg, G. D. (2005) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30087 · Cited by 79 · see citing works
Epigenetics, a key for unlocking complex CNS disorders? Therapeutic implications
Szyf, M. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.01.009 · Cited by 76 · see citing works
Early-Onset Alzheimer Disease in Families With Late-Onset Alzheimer Disease: A Potential Important Subtype of Familial Alzheimer Disease
Brickell, K. L., Steinbart, E. J., Rumbaugh, M., Payami, H., Schellenberg, G. D., Van Deerlin, V., Yuan, W., & Bird, T. D. (2006) · Archives of Neurology · doi:10.1001/archneur.63.9.1307 · Cited by 77 · see citing works
Function and Dysfunction of the Presenilins
Sisodia, S. S., Kim, S. H., & Thinakaran, G. (1999) · The American Journal of Human Genetics · doi:10.1086/302475 · Cited by 76 · see citing works
Relation of genomic variants for Alzheimer disease dementia to common neuropathologies
Farfel, J. M., Yu, L., Buchman, A. S., Schneider, J. A., De Jager, P. L., & Bennett, D. A. (2016) · Neurology · doi:10.1212/wnl.0000000000002909 · Cited by 64 · see citing works
A novel mechanism for the regulation of amyloid precursor protein metabolism
Chen, Q., Kimura, H., & Schubert, D. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200110151 · Cited by 63 · see citing works
Blood cell-produced amyloid-β induces cerebral Alzheimer-type pathologies and behavioral deficits
Sun, H.-L., Chen, S.-H., Yu, Z.-Y., Cheng, Y., Tian, D.-Y., Fan, D.-Y., He, C.-Y., Wang, J., Sun, P.-Y., Chen, Y., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0842-1 · Cited by 56 · see citing works
Central and peripheral circadian clocks and their role in Alzheimer's disease
Chauhan, R., Chen, K.-F., Kent, B. A., & Crowther, D. C. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.030627 · Cited by 58 · see citing works
“Genetic linkage studies in familial AD (Goate et al., 1991; Rogaev et al., 1995; Sherrington et al., 1995) and wholegenome studies of the more common, sporadic form of AD (Jonsson et al.”
Background
Ocular manifestations of Alzheimer's disease in animal models
Parnell, M., Guo, L., Abdi, M., & Cordeiro, M. F. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/786494 · Cited by 56 · see citing works
Is sleep disruption a risk factor for Alzheimer's disease?
Macedo, A. C., Balouch, S., & Tabet, N. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-161287 · Cited by 49 · see citing works
Association study of two genetic variants in mitochondrial transcription factor A (TFAM) in Alzheimer's and Parkinson's disease
Belin, A. C., Björk, B. F., Westerlund, M., Galter, D., Sydow, O., Lind, C., Pernold, K., Rosvall, L., Håkansson, A., Winblad, B., et al. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.05.010 · Cited by 48 · see citing works
Clinical, biological, and imaging features of monogenic Alzheimer’s disease
Pilotto, A., Padovani, A., & Borroni, B. (2013) · BioMed Research International · doi:10.1155/2013/689591 · Cited by 47 · see citing works
New precision medicine avenues to the prevention of Alzheimer’s disease from insights into the structure and function of γ-secretases
De Strooper, B., & Karran, E. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00057-w · Cited by 36 · see citing works
Evidence for three loci modifying age‐at‐onset of Alzheimer's disease in early‐onset PSEN2 families
Marchani, E. E., Bird, T. D., Steinbart, E. J., Rosenthal, E., Yu, C., Schellenberg, G. D., & Wijsman, E. M. (2010) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31072 · Cited by 29 · see citing works

Calsenilin: A calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment
Buxbaum, J. D., Choi, E., Luo, Y., Lilliehöök, C., Crowley, A. C., Merriam, D. E., & Wasco, W. (1998) · Nature Medicine · doi:10.1038/2673 · Cited by 341 · see citing works
Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1
Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.-M., Pérez‐Tur, J., Hutton, M., Buée, L., Harigaya, Y., Yager, D., et al. (1996) · Nature · doi:10.1038/383710a0 · Cited by 1,453 · see citing works
Evaluation of cancer related missense mutations in CENPH
Sucularlı, C. (2019) · Acta Medica · doi:10.32552/2019.actamedica.385
Mechanisms of cell death in Alzheimer's disease: Role of presenilins
Popescu, B. O., & Ankarcrona, M. (2004) · Journal of Alzheimer s Disease · doi:10.3233/jad-2004-6203 · Cited by 20 · see citing works
Apoptotic Activities of Wild-Type and Alzheimer's Disease-Related Mutant Presenilins in Drosophila melanogaster
Ye, Y., & Fortini, M. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.146.6.1351 · Cited by 107 · see citing works

Authors: Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holman, K., Tsuda, T., Mar, L., Sorbi, S., Nacmias, B., Piacentini, S., Amaducci, L., Chumakov, I., Cohen, D., Lannfelt, L., Fraser, P. E., Rommens, J. M., & George-Hyslop, P. H. S.
Affiliations: University of Toronto (CA)
University of Florence (IT)
Fondation Jean Dausset-CEPH (FR)
Karolinska Institutet (SE)
ORCID: Rogaev, E. I.
Rogaeva, E. A.
Ikeda, M.
Liang, Y.
Lin, C.
Tsuda, T.
Sorbi, S.
Nacmias, B.
Piacentini, S.
Cohen, D.
Lannfelt, L.
Rommens, J. M.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1995-08
Volume: 376
Issue: 6543
Pages: 775-778
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/376775a0
OpenAlex: W2045153164
Cited by: 2,052
References: 8
Citations by year: 2026: 12 · 2025: 29 · 2024: 36 · 2023: 36 · 2022: 44 · 2021: 56 · 2020: 54 · 2019: 51 · 2018: 50 · 2017: 66 · 2016: 52 · 2015: 48 · 2014: 53 · 2013: 48 · 2012: 70
FWCI: 71.57
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Florence Research (University of Florence) (submittedVersion)
Funders: Canadian Institutes of Health Research (37920)
National Institute on Aging (P30AG010133, P30 AG-10133, U24AG021886)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: familial Alzheimer's disease, presenilin, chromosome 1, missense mutations, early-onset Alzheimer's disease, late-onset Alzheimer's disease, transmembrane proteins, gene cloning
MeSH terms: Alzheimer Disease, Amino Acid Sequence, Base Sequence, Chromosomes, Human, Pair 1, DNA, Humans, Membrane Proteins, Molecular Sequence Data, Mutation, Sequence Homology, Amino Acid, Presenilin-1, Presenilin-2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks