A4POE*4-associated Alzheimer's disease risk is modified by α1–antichymotrypsin polymorphism

Kamboh, M. Ilyas; Sanghera, Dharambir K.; Ferrell, Robert E.; DeKosky, Steven T.

doi:10.1038/ng0895-486

Cited by 336Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

A4POE*4-associated Alzheimer's disease risk is modified by α1–antichymotrypsin polymorphism

Kamboh, M. Ilyas, Sanghera, Dharambir K., Ferrell, Robert E., DeKosky, Steven T.·1995·Nature Genetics

DOI 10.1038/ng0895-486

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Abstract

Genetic studies on Alzheimer's disease (AD), a devastating neurodegenerative disorder, have identified the apolipoprotein E (APOE) gene as a strong susceptibility marker for AD. The E*4 allele of APOE is a major risk factor for AD regardless of age of onset or family history. However, the observation that the APOE*4 allele is neither necessary nor sufficient for the expression of AD emphasizes the involvement of other environmental or genetic elements that, either in conjunction with APOE*4 or alone, increase an individual's risk of developing AD. Among the candidate genes that may affect the risk of this multifactorial disease is the gene coding for alpha 1-antichymotrypsin (ACT). Like APOE protein, ACT binds to beta-amyloid peptide (A beta P) with high affinity in the filamentous deposits found in the AD brain and serves as a strong stimulatory factor in the polymerization of A beta P into amyloid filaments. In AD brains, ACT expression is enhanced, particularly in areas that develop amyloid plaques, suggesting that ACT may play an important role in the pathogenesis of AD. Here we show that a common polymorphism in the signal peptide of ACT confers a significant risk for AD. Furthermore, the APOE*4 gene dosage effect associated with AD risk is significantly modified by the ACT polymorphism. We have also identified a unique combination of the ACT/AA and APOE 4/4 genotypes as a potential susceptibility marker for AD, as its frequency was 1/17 in the AD group compared to 1/313 in the general population control. Our data show that ACT behaves as a modifier gene that alters the AD risk conventionally associated with the APOE*4 allele.

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The findings extend earlier work in mouse Aβ aggregation models that pointed to a pathogenic role for C4b and Serpina3n, and genetic evidence connecting human SERPINA3 with AD risk.
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Clinical diagnosis of Alzheimer's disease: Report of the NINCDS‐ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Part II. Standardization of the neuropathologic assessment of Alzheimer's disease
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268 · see citing works
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786 · see citing works
Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
Fillenbaum, G., & Heyman, A. (2002) · doi:10.1002/0470846410.ch42(iii · Cited by 2,859 · see citing works
Diagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499 · see citing works
The Clinical Diagnosis of Alzheimer's Disease
Wade, J. P. H., Mirsen, T. R., Hachinski, V. C., Fisman, M., Lau, C. S., & Merskey, H. (1987) · Archives of Neurology · doi:10.1001/archneur.1987.00520130016010 · Cited by 1,416 · see citing works
Immunochemical identification of the serine protease inhibitor α1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease
Abraham, C. R., Selkoe, D. J., & Potter, H. (1988) · Cell · doi:10.1016/0092-8674(88)90462-x · Cited by 893 · see citing works
Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments
Ma, J., Yee, A., Brewer, H. B., Das, S., & Potter, H. (1994) · Nature · doi:10.1038/372092a0 · Cited by 871 · see citing works
Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro.
(1994) · PubMed Central · Cited by 441 · see citing works
Hypothesis: Microtubule Instability and Paired Helical Filament Formation in the Alzheimer Disease Brain Are Related to Apolipoprotein E Genotype
Strittmatter, W. J., Weisgraber, K. H., Goedert, M., Saunders, A. M., Huang, D., Corder, E. H., Dong, L., Jakes, R., Alberts, M. J., Gilbert, J. R., et al. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1019 · Cited by 433 · see citing works
Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3
Sanan, D. A., Weisgraber, K. H., Russell, S. J., Mahley, R. W., Huang, D., Saunders, A., Schmechel, D., Wisniewski, T., Frangione, B., & Roses, A. D. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117407 · Cited by 404 · see citing works
Unity in Function in the Absence of Consensus in Sequence: Role of Leader Peptides in Export
Randall, L. L., & HARDY, S. J. S. (1989) · Science · doi:10.1126/science.2646712 · Cited by 222 · see citing works
α1-Antichymotrypsin is associated solely with amyloid deposits containing the β-protein. Amyloid and cell localization of α1-antichymotrypsin
Abraham, C. R., Shirahama, T., & Potter, H. (1990) · Neurobiology of Aging · doi:10.1016/0197-4580(90)90045-2 · Cited by 150 · see citing works
α1‐Antichymotrypsin as a possible biochemical marker for Alzheimer‐type dementia
Matsubara, E., Hirai, S., Amari, M., Shoji, M., Yamaguchi, H., Okamoto, K., Ishiguro, K., Harigaya, Y., & Wakabayashi, K. (1990) · Annals of Neurology · doi:10.1002/ana.410280414 · Cited by 146 · see citing works
α1‐Antichymotrypsin Binding to Alzheimer Aβ Peptides Is Sequence Specific and Induces Fibril Disaggregation In Vitro
Fraser, P. E., Nguyen, J. T., McLachlan, D. R. C., Abraham, C. R., & Kirschner, D. A. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03568.x · Cited by 137 · see citing works
Apolipoprotein E polymorphism and susceptibility to Alzheimer's disease.
Kamboh, M. I. (1995) · PubMed · Cited by 105 · see citing works
Self-citation
The relationship of APOE polymorphism and cholesterol levels in normoglycemic and diabetic subjects in a biethnic population from the San Luis Valley, Colorado
Kamboh, M. I. (1995) · Atherosclerosis · doi:10.1016/0021-9150(94)05409-c · Cited by 104 · see citing works
Self-citation
Distribution pattern and functional state of ?1-antichymotrypsin in plaques and vascular amyloid in Alzheimer's disease
Rozemüller, A. J. M., Abbink, J. J., Kamp, A. M., Stam, F. C., Hack, C. E., & Eikelenboom, P. (1991) · Acta Neuropathologica · doi:10.1007/bf00294446 · Cited by 97 · see citing works
The molecular basis of α1-antichymotrypsin deficiency in a heterozygote with liver and lung disease
Faber, J.-P., Poller, W. C., Olek, K., Baumann, U., Carlson, J. A., Lindmark, B., & Eriksson, S. (1993) · Journal of Hepatology · doi:10.1016/s0168-8278(05)80275-2 · Cited by 93 · see citing works
Distribution of the Protease Inhibitor α1-Antichymotrypsin in Cerebral and Systemic Amyloid
Picken, M. M., Larrondo-Lillo, M., Coria, F., Gallo, G. R., Shelanski, M. L., & Frangione, B. (1990) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199001000-00005 · Cited by 65 · see citing works
Alpha 1-antichymotrypsin is present in diffuse senile plaques. A comparative study of beta-protein and alpha 1-antichymotrypsin immunostaining in the Alzheimer brain.
Shoji, M., Hirai, S., Yamaguchi, H., Harigaya, Y., Ishiguro, K., & Matsubara, E. (1991) · PubMed Central · Cited by 63 · see citing works
Phenotypic effects of apolipoprotein structural variation on lipid profiles. III. Contribution of apolipoprotein E phenotype to prediction of total cholesterol, apolipoprotein B, and low density lipoprotein cholesterol in the healthy women study.
Eichner, J. E., Kuller, L. H., Ferrell, R. E., Meilahn, E. N., & Kamboh, M. I. (1990) · Arteriosclerosis An Official Journal of the American Heart Association Inc · doi:10.1161/01.atv.10.3.379 · Cited by 54 · see citing works
Self-citation
Differential expression of α 1-antichymotrypsin in the aged human brain
Ishiguro, K., Shoji, M., Yamaguchi, H., Matsubara, E., Ikeda, M., Kawarabayashi, T., Harigaya, Y., Okamoto, K., & Hirai, S. (1993) · Virchows Archiv B Cell Pathology Including Molecular Pathology · doi:10.1007/bf02915116 · Cited by 10 · see citing works
Characterization of the Serpin, α1‐Antichymotrypsin, in Normal Human Cerebrospinal Fluid
Rayford, A., Rao, J. S., & Festoff, B. W. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09281.x · Cited by 10 · see citing works
Proteinase inhibitor α1-antichymotrypsin has different expression in various forms of neuronal ceroid lipofuscinosis
Wisniewski, K. E., & Kida, E. (1990) · Experimental Neurology · doi:10.1016/0014-4886(90)90056-x · Cited by 8 · see citing works

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Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease
Zhou, Y., Song, W. M., Andhey, P. S., Swain, A., Levy, T., Miller, K. R., Poliani, P. L., Cominelli, M., Grover, S., Gilfillan, S., et al. (2020) · Nature Medicine · doi:10.1038/s41591-019-0695-9 · Cited by 1,150 · see citing works
Inflammatory processes in Alzheimer's disease
Heneka, M. T., & O'Banion, M. K. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.11.017 · Cited by 782 · see citing works
Neuroinflammatory processes in Alzheimer’s disease
Heneka, M. T., O’Banion, M. K., Terwel, D., & Kummer, M. P. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0438-z · Cited by 433 · see citing works
Association between features of the insulin resistance syndrome and alzheimer's disease independently of apolipoprotein e4 phenotype: cross sectional population based study
Kuusisto, J., Koivisto, K. J., Mykkänen, L. M., Helkala, E.-L., Vanhanen, M., Hänninen, T., Kervinen, K., Kesäniemi, Y. A., Riekkinen, P. J., & Laakso, M. (1997) · BMJ · doi:10.1136/bmj.315.7115.1045 · Cited by 426 · see citing works
Contribution of inflammatory processes to Alzheimer's disease: molecular mechanisms
Sastre, M., Klockgether, T., & Heneka, M. T. (2006) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2005.11.014 · Cited by 426 · see citing works
ALZHEIMER'S DISEASE: Genetic Studies and Transgenic Models
Price, D. L., Tanzi, R. E., Borchelt, D. R., & Sisodia, S. S. (1998) · Annual Review of Genetics · doi:10.1146/annurev.genet.32.1.461 · Cited by 406 · see citing works
Neuroinflammation in Alzheimer's disease and prion disease
Eikelenboom, P., Bate, C., van Gool, W., Hoozemans, J., Rozemuller, J., Veerhuis, R., & Williams, A. (2002) · Glia · doi:10.1002/glia.10146 · Cited by 400 · see citing works
Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation.
Cuppens, H., Lin, W., Jaspers, M., Costes, B., Teng, H., Vankeerberghen, A., Jorissen, M., Droogmans, G., Reynaert, I., Goossens, M., et al. (1998) · Journal of Clinical Investigation · doi:10.1172/jci639 · Cited by 393 · see citing works
Nonsteroidal Anti-Inflammatory Drugs and Peroxisome Proliferator-Activated Receptor-γ Agonists Modulate Immunostimulated Processing of Amyloid Precursor Protein through Regulation of β-Secretase
Sastre, M., Dewachter, I., Landreth, G. E., Willson, T. M., Klockgether, T., LEUVEN, F. V., & Heneka, M. T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-30-09796.2003 · Cited by 359 · see citing works
A full genome scan for late onset Alzheimer's disease
Kehoe, P. G. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.2.237 · Cited by 356 · see citing works
Review: Systemic inflammation and<scp>A</scp>lzheimer's disease
Holmes, C. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01307.x · Cited by 356 · see citing works
Naturally occurring phytochemicals for the prevention of Alzheimer’s disease
Kim, J., Lee, H. J., & Lee, K. W. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06562.x · Cited by 354 · 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
Microglia Function in Alzheimer’s Disease
Solito, E., & Sastre, M. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00014 · Cited by 347 · see citing works
Cholinergic dysfunction in diseases with Lewy bodies
Dodel, R. C., Du, Y.-S., Bales, K., Gao, F., Eastwood, B., Glazier, B., Zimmer, R., Cordell, B., Hake, A., Evans, R., et al. (2000) · Neurology · doi:10.1212/wnl.54.2.407 · Cited by 972 · see citing works
Causative and susceptibility genes for Alzheimer’s disease: a review
Rocchi, A., Pellegrini, S., Siciliano, G., & Murri, L. (2003) · Brain Research Bulletin · doi:10.1016/s0361-9230(03)00067-4 · Cited by 319 · see citing works
Human Whole-Genome Shotgun Sequencing
Weber, J. L., & Myers, E. W. (1997) · Genome Research · doi:10.1101/gr.7.5.401 · Cited by 311 · see citing works
β-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer's disease
Cummings, B. J., Pike, C. J., Shankle, R., & Cotman, C. W. (1996) · Neurobiology of Aging · doi:10.1016/s0197-4580(96)00170-4 · Cited by 305 · see citing works
Neuroglia in neurodegeneration
Heneka, M. T., Rodriguez, J. J., & Verkhratsky, A. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2009.11.004 · Cited by 303 · see citing works
Molecular genetics of Alzheimer’s disease
George‐Hyslop, P. S. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00301-7 · Cited by 276 · see citing works
Statement on Use of Apolipoprotein E Testing for Alzheimer Disease
Farrer, L. A. (1995) · JAMA · doi:10.1001/jama.1995.03530200063039 · Cited by 271 · see citing works
Genetic association between intronic polymorphism in presenilin-1 gene and late-onset Alzheimer's disease
Wragg, M. A., Talbot, C. J., Hutton, M., & Goate, A. (1996) · The Lancet · doi:10.1016/s0140-6736(96)91140-x · Cited by 243 · see citing works
Apolipoprotein E genotyping in Alzheimer's disease
Relkin, N. R. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90284-6 · Cited by 241 · 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
Glial activation in Alzheimer's disease: the role of AÎ² and its associated proteins
Meda, L. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00307-4 · Cited by 222 · see citing works
Alzheimer Presenilins in the Nuclear Membrane, Interphase Kinetochores, and Centrosomes Suggest a Role in Chromosome Segregation
Li, J., Xu, M., Zhou, H., Ma, J., & Potter, H. (1997) · Cell · doi:10.1016/s0092-8674(00)80356-6 · Cited by 218 · see citing works
The Toxicity of the Alzheimer's β-Amyloid Peptide Correlates with a Distinct Fiber Morphology
Seilheimer, B., Bohrmann, B., Bondolfi, L., Müller, F., Stüber, D., & Döbeli, H. (1997) · Journal of Structural Biology · doi:10.1006/jsbi.1997.3859 · Cited by 207 · see citing works
Increased Brain β-Amyloid Load, Phosphorylated Tau, and Risk of Alzheimer Disease Associated With an Intronic CYP46 Polymorphism
Papassotiropoulos, A., Streffer, J. R., Tsolaki, M., Schmid, S., Thal, D. R., Nicosia, F. M., Iakovidou, V., Maddalena, A. S., Lütjohann, D., Ghebremedhin, E., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.1.29 · Cited by 208 · see citing works
Identification of Novel Genes in Late-Onset Alzheimer's Disease
Pericak‐Vance, M. A., Grubber, J. M., Bailey, L., Hedges, D. J., West, S. G., Santoro, L., Kemmerer, B., Hall, J. L., Saunders, A. M., Roses, A. D., et al. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00196-0 · Cited by 195 · see citing works
Association of an interleukin 1α polymorphism with Alzheimer’s disease
Du, Y., Dodel, R. C., Eastwood, B. J., Bales, K. R., Gao, F., Lohmüller, F., Müller, U., Kurz, A., Zimmer, R., Evans, R. M., et al. (2000) · Neurology · doi:10.1212/wnl.55.4.480 · Cited by 195 · see citing works
SNP association studies in Alzheimer's disease highlight problems for complex disease analysis
Emahazion, T. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(01)02342-3 · Cited by 180 · see citing works
Deficiency in Mitochondrial Aldehyde Dehydrogenase Increases the Risk for Late-Onset Alzheimer's Disease in the Japanese Population
Kamino, K., Nagasaka, K., Imagawa, M., Yamamoto, H., Yoneda, H., Ueki, A., Kitamura, S., Namekata, K., Miki, T., & Ohta, S. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2923 · Cited by 173 · see citing works
Interactions between APP secretases and inflammatory mediators
Sastre, M., Walter, J., & Gentleman, S. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-25 · Cited by 172 · 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
Self-citation
Molecular genetics of Alzheimer's disease
Cruts, M., & Broeckhoven, C. V. (1998) · Annals of Medicine · doi:10.3109/07853899809002605 · Cited by 148 · see citing works
Oxidative stress and neuroinflammation in Alzheimer's disease and amyotrophic lateral sclerosis: Common links and potential therapeutic targets
Mhatre, M., Floyd, R. A., & Hensley, K. (2004) · Journal of Alzheimer s Disease · doi:10.3233/jad-2004-6206 · Cited by 147 · see citing works
Neuroinflammation and anti-inflammatory therapy for Alzheimer’s disease
Moore, A. H., & O’Banion, M. K. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00162-x · Cited by 146 · see citing works
α-1-Antichymotrypsin Promotes β-Sheet Amyloid Plaque Deposition in a Transgenic Mouse Model of Alzheimer's Disease
Nilsson, L. N. G., Bales, K. R., DiCarlo, G., Gordon, M. N., Morgan, D., Paul, S. M., & Potter, H. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01444.2001 · Cited by 137 · see citing works
Analysis of genetic polymorphisms in the transforming growth factor-β1 gene and the risk of Alzheimer's disease
Luedecking‐Zimmer, E., DeKosky, S. T., Mehdi, H., Ganguli, M., & Kamboh, M. I. (2000) · Human Genetics · doi:10.1007/s004390000313 · Cited by 137 · see citing works
Self-citation
Blood Levels of Alpha-1-Antichymotrypsin and Risk Factors for Alzheimer’s Disease: Effects of Gender and Apolipoprotein E Genotype
Licastro, F., Masliah, E., Pedrini, S., & Thal, L. J. (2000) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017209 · Cited by 137 · see citing works
Effect of Age, Ethnicity, and Head Injury on the Association between APOE Genotypes and Alzheimer's Disease
TANG, M., Maestre, G. E., TSAI, W., Liu, X., FENG, L., Chung, W., Chun, M. R., Schofield, P. W., Stern, Y., Tycko, B., et al. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb32593.x · Cited by 134 · see citing works
Dementia with Lewy bodies
McKeith, I. G., Burn, D. J., Ballard, C. G., Collerton, D., Jaros, E., Morris, C. M., McLaren, A., Perry, E. K., Perry, R., Piggott, M. A., et al. (2003) · Seminars in Clinical Neuropsychiatry · doi:10.1053/scnp.2003.50006 · Cited by 134 · see citing works
Pathophysiology of Alzheimer's Disease
Imbimbo, B. P., Lombard, J., & Pomara, N. (2005) · Neuroimaging Clinics of North America · doi:10.1016/j.nic.2005.09.009 · Cited by 133 · see citing works
NSAID and Antioxidant Prevention of Alzheimer's Disease: Lessons from <i>In Vitro</i> and Animal Models
COLE, G. M., MORIHARA, T., LIM, G. P., YANG, F., BEGUM, A., & FRAUTSCHY, S. A. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1332.005 · Cited by 129 · see citing works
Apolipoprotein E Genetic Variation and Alzheimer’s Disease
Rubinsztein, D. C., & Easton, D. F. (1999) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017120 · Cited by 151 · see citing works
Epistasis in sporadic Alzheimer's disease
Combarros, O., Cortina‐Borja, M., Smith, A. D., & Lehmann, D. J. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.027 · Cited by 123 · see citing works
Alpha1-antichymotrypsin, an inflammatory protein overexpressed in Alzheimer's disease brain, induces tau phosphorylation in neurons
Padmanabhan, J., Levy, M. M., Dickson, D. W., & Potter, H. (2006) · Brain · doi:10.1093/brain/awl255 · Cited by 123 · see citing works
Interleukin-1 and the Immunogenetics of Alzheimer Disease
Mrak, R. E., & Griffin, W. S. T. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.6.471 · Cited by 119 · see citing works
Dementia with Lewy Bodies. A Distinct Non‐Alzheimer Dementia Syndrome?
Ince, P. G., Perry, E. K., & Morris, C. M. (1998) · Brain Pathology · doi:10.1111/j.1750-3639.1998.tb00156.x · Cited by 115 · see citing works
A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer’s disease
Crawford, F., Freeman, M. J., Schinka, J. A., Abdullah, L. I., Gold, M., Hartman, R. D., Krivian, K., Morris, M. D., Richards, D., Duara, R., et al. (2000) · Neurology · doi:10.1212/wnl.55.6.763 · Cited by 109 · see citing works
Alzheimer Aβ neurotoxicity: Promotion by antichymotrypsin, ApoE4; inhibition by Aβ-related peptides
Ma, J., Brewer, H. B., & Potter, H. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(96)00112-1 · Cited by 108 · see citing works
The Murine Orthologue of Human Antichymotrypsin
Horvath, A. J., Irving, J. A., Rossjohn, J., Law, R. H. P., Bottomley, S., Quinsey, N. S., Pike, R. N., Coughlin, P., & Whisstock, J. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505598200 · Cited by 107 · see citing works
α1-antichymotrypsin
Kalsheker, N. A. (1996) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/1357-2725(96)00032-5 · Cited by 105 · see citing works
Apolipoprotein E genotype in patients with alzheimer's disease: Implications for the risk of dementia among relatives
Farrer, L. A., Cupples, L. A., van Duijn, C. M., Kurz, A., Zimmer, R., Müller, U., Green, R. C., Clarke, V., Shoffner, J. M., Wallace, D. C., et al. (1995) · Annals of Neurology · doi:10.1002/ana.410380515 · Cited by 100 · see citing works
Association of transferrin C2 allele with late-onset Alzheimer's disease
Namekata, K., Imagawa, M., Terashi, A., Ohta, S., Oyama, F., & Ihara, Y. (1997) · Human Genetics · doi:10.1007/s004390050600 · Cited by 100 · see citing works
Plasma and cerebrospinal fluid α1‐antichymotrypsin levels in Alzheimer's disease: Correlation with cognitive impairment
DeKosky, S. T., Ikonomović, M. D., Wang, X., Farlow, M. R., Wisniewski, S. R., López, O. L., Becker, J. T., Saxton, J. A., Klunk, W. E., Sweet, R. A., et al. (2002) · Annals of Neurology · doi:10.1002/ana.10414 · Cited by 97 · see citing works
Self-citation
Genetic polymorphisms in the cathespin D and interleukin-6 genes and the risk of Alzheimer's disease
Bhojak, T., DeKosky, S. T., Ganguli, M., & Kamboh, M. I. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01185-x · Cited by 94 · see citing works
Self-citation
Bleomycin hydrolase is associated with risk of sporadic Alzheimer's disease
Montoya, S. E., Aston, C. E., DeKosky, S. T., Kamboh, M. I., Lazo, J. S., & Ferrell, R. E. (1998) · Nature Genetics · doi:10.1038/ng0398-211 · Cited by 91 · see citing works
Self-citation
Risk Factors for Cerebral Amyloid Angiopathy in the Elderly
Yamada, M. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04797.x · Cited by 88 · see citing works
Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid formation
Nilsson, L. N. G., Arendash, G. W., Leighty, R. E., Costa, D. A., Low, M. A., Garcia, M. F., Cracciolo, J. R., Rojiani, A. M., Wu, X., Bales, K. R., et al. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.12.011 · Cited by 87 · see citing works
The inflammation-induced pathological chaperones ACT and apo-E are necessary catalysts of Alzheimer amyloid formation
Potter, H. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00308-6 · Cited by 87 · see citing works
Association of the mitochondrial tRNAA4336G mutation with Alzheimer's and Parkinson's diseases
Egensperger, R., Kösel, S., Schnopp, N. M., Mehraein, P., & Graeber, M. B. (1997) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1997.tb01301.x · Cited by 90 · see citing works
Plasma levels of apolipoprotein E and genetic markers in elderly patients with Alzheimer's disease
Scacchi, R., Gambina, G., Ruggeri, M., Martini, M. C., Ferrari, G., Silvestri, M., Schiavon, R., & Corbo, R. M. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00889-1 · Cited by 83 · see citing works
Genetic variation in the cholesterol 24-hydroxylase (CYP46) gene and the risk of Alzheimer's disease
Desai, P. P., DeKosky, S. T., & Kamboh, M. I. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00443-3 · Cited by 83 · see citing works
Self-citation
Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age‐matched controls
Perry, R. T., Collins, J. S., Harrell, L. E., Acton, R. T., & Go, R. C. P. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1371 · Cited by 81 · see citing works
Molecular genetics of Alzheimerʼs disease: the role of β-amyloid and the presenilins
Tandon, A., Rogaeva, E. A., MULLAN, M. J., & George‐Hyslop, P. S. (2000) · Current Opinion in Neurology · doi:10.1097/00019052-200008000-00003 · Cited by 80 · see citing works
Genetic association studies between Alzheimer's disease and two polymorphisms in the low density lipoprotein receptor-related protein gene
Kamboh, M. I., Ferrell, R. E., & DeKosky, S. T. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00141-4 · Cited by 79 · see citing works
Self-citation
Association between the low density lipoprotein receptor-related protein (LRP) and Alzheimer's disease
Wavrant-DeVrièze, F., Pérez‐Tur, J., Lambert, J., Frigard, B., Pasquier, F., Delacourte, A., Amouyel, P., Hardy, J., & Chartier‐Harlin, M. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00304-2 · Cited by 77 · see citing works
Serpin Signatures in Prion and Alzheimer’s Diseases
Zattoni, M., Mearelli, M., Vanni, S., Baldeschi, A. C., Tran, T. H., Ferracin, C., Catania, M., Moda, F., Fede, G. D., Giaccone, G., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02817-3 · Cited by 74 · see citing works
Genetic risk factors in Alzheimer's disease.
Tilley, L. A., Morgan, K., & Kalsheker, N. A. (1998) · Molecular Pathology · doi:10.1136/mp.51.6.293 · Cited by 71 · see citing works
Natural Compounds and Plant Extracts as Therapeutics Against Chronic Inflammation in Alzheimer’s Disease – A Translational Perspective
Apetz, N., Münch, G. W., Govindaraghavan, S., & Gyengési, E. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666140917110635 · Cited by 72 · see citing works
Familial idiopathic basal ganglia calcification (Fahr's disease) without neurological, cognitive and psychiatric symptoms is not linked to the IBGC1 locus on chromosome 14q
Brodaty, H., Mitchell, P. B., Luscombe, G. M., Kwok, J. B., Badenhop, R. F., McKenzie, R., & Schofield, P. R. (2001) · Human Genetics · doi:10.1007/s00439-001-0650-x · Cited by 71 · see citing works
Complement activation as a biomarker for Alzheimer's disease
Aiyaz, M., Lupton, M. K., Proitsi, P., Powell, J. F., & Lovestone, S. (2011) · Immunobiology · doi:10.1016/j.imbio.2011.07.023 · Cited by 69 · see citing works
The National Institute on Aging/Alzheimer's Association Recommendations on the Application of Apolipoprotein E Genotyping to Alzheimer's Diseasea
Relkin, N. R., Kwon, Y. J., Tsai, J., & Gandy, S. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb32608.x · Cited by 69 · see citing works
Review of the next generation of Alzheimer's disease therapeutics: challenges for drug development
Cutler, N. R., & Sramek, J. J. (2001) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(00)00147-0 · Cited by 67 · see citing works
CSF beta-amyloid, cognition, and APOE genotype in Alzheimer’s disease
Samuels, S., Silverman, J. M., Marin, D. B., Peskind, E. R., Younki, S. G., Greenberg, D. A., Schnur, E., Santoro, J., & Davis, K. L. (1999) · Neurology · doi:10.1212/wnl.52.3.547 · Cited by 67 · see citing works
Gene-Environment Interaction in Alzheimer’s Disease:A Potential Role for Cholesterol
Chandra, V., & Pandav, R. S. (1998) · Neuroepidemiology · doi:10.1159/000026175 · Cited by 66 · see citing works
α2 Macroglobulin and the risk of Alzheimer’s disease
Dodel, R. C., Du, Y., Bales, K. R., Gao, F., Eastwood, B. J., Glazier, B. S., Zimmer, R., Cordell, B., Hake, A. M., Evans, R. M., et al. (2000) · Neurology · doi:10.1212/wnl.54.2.438 · Cited by 66 · see citing works
Cortical beta amyloid protein triggers an immune response, but no synaptic changes in the APPswe/PS1dE9 Alzheimer's disease mouse model
Wirz, K. T. S., Bossers, K., Stargardt, A., Kamphuis, W., Swaab, D. F., Hol, E. M., & Verhaagen, J. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.11.008 · Cited by 65 · see citing works
APOE, ACT and CHRNA7 genes in the conversion from amnestic mild cognitive impairment to Alzheimer's disease
Barabash, A., Marcos, A., Ancín, I., Vázquez-Álvarez, B., de Ugarte, C., Gil, P., Fernández, C., Encinas, M., López-Ibor, J. J., & Cabranes, J. A. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.003 · Cited by 65 · see citing works
The PSEN1, p.E318G Variant Increases the Risk of Alzheimer's Disease in APOE-ε4 Carriers
Benítez, B. A., Karch, C. M. M., Cai, Y., Jin, S. C., Cooper, B., Carrell, D., Bertelsen, S. E., Chibnik, L. B., Schneider, J. A., Bennett, D., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003685 · Cited by 64 · see citing works
Analysis of Separate and Combined Effects of Common Variation in KCNJ11 and PPARG on Risk of Type 2 Diabetes
Hansen, S. K., Nielsen, E.-M. D., Ek, J., Andersen, G., Glümer, C., Carstensen, B., Mouritzen, P., Drivsholm, T., Borch‐Johnsen, K., Jørgensen, T., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1942 · Cited by 61 · see citing works
The Neurobiology and Pharmacotherapy of Alzheimer's Disease
Félician, O., & Sandson, T. A. (1999) · Journal of Neuropsychiatry · doi:10.1176/jnp.11.1.19 · Cited by 61 · see citing works
Alpha-1-antichymotrypsin (ACT or SERPINA3) polymorphism may affect age-at-onset and disease duration of Alzheimer's disease
Kamboh, M. I., Minster, R. L., Kenney, M., Öztürk, A., Desai, P. P., Kammerer, C. M., & DeKosky, S. T. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.07.015 · Cited by 60 · see citing works
Self-citation
Inflammatory Risk Factors and Pathologies Associated with Alzheimers Disease
Sastre, M., Richardson, J. C., Gentleman, S., & Brooks, D. J. (2011) · Current Alzheimer Research · doi:10.2174/156720511795256062 · Cited by 58 · see citing works
Using meta-analysis to explain the diversity of results in genetic studies of late-onset Alzheimer's disease and to identify high-risk subgroups.
Lehmann, D., Williams, J., McBroom, J., & Smith, A. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00464-x · Cited by 63 · see citing works
Pharmacogenomics of neurodegenerative diseases
Maimone, D., Dominici, R., & Grimaldi, L. M. E. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00939-0 · Cited by 56 · see citing works
Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury
Castranio, E. L., Mounier, A., Wolfe, C. M., Nam, K. N., Fitz, N. F., Letronne, F., Schug, J., Koldamova, R. P., & Lefterov, I. M. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.05.006 · Cited by 55 · see citing works
Widespread neuronal expression of the presenilin-1 early-onset Alzheimer's disease gene in the murine brain.
Cribbs, D. H., Chen, L.-S., Bende, S. M., & LaFerla, F. M. (1996) · Europe PMC (PubMed Central) · Cited by 55 · see citing works
Identification and expression analysis of a potential familial Alzheimer disease gene on chromosome 1 related to AD3.
Li, J., Ma, J., & Potter, H. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.26.12180 · Cited by 56 · see citing works
The genetics of Alzheimer’s disease
Schellenberg, G. D., D’Souza, I., & Poorkaj, P. (2000) · Current Psychiatry Reports · doi:10.1007/s11920-000-0061-z · Cited by 55 · see citing works
High Expression of Apolipoprotein E mRNA in the Brains with Sporadic Alzheimer’s Disease
Yamagata, K., Urakami, K., Ikeda, K., Ji, Y., Adachi, Y., Arai, H., Sasaki, H., Sato, K., & Nakashima, K. (2001) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000051236 · Cited by 53 · see citing works
Cerebral amyloid angiopathies.
Coria, F., & Rubio, I. (1996) · PubMed · Cited by 53 · see citing works
Genetics of inclusion‐body myositis
Needham, M., Mastaglia, F. L., & Garlepp, M. J. (2007) · Muscle & Nerve · doi:10.1002/mus.20766 · Cited by 51 · see citing works
ACT and UCH‐L1 polymorphisms in Parkinson's disease and age of onset
Wang, J., Zhao, C., Si, Y.-M., Liu, Z., Chen, B., & Yu, L. (2002) · Movement Disorders · doi:10.1002/mds.10179 · Cited by 51 · see citing works
Molecular and cellular mediators of Alzheimer's disease inflammation
Strohmeyer, R., & Rogers, J. (2001) · Journal of Alzheimer s Disease · doi:10.3233/jad-2001-3118 · Cited by 51 · see citing works
Oxidative-stress associated parameters (lactoferrin, superoxide dismutases) in serum of patients with Alzheimer's disease
Thome, J., Gsell, W., Rösier, M., Kornhuber, J., Frölich, L., Hashimoto, E., Zielke, B., Wiesbeck, G. A., & Riedcrer, P. (1996) · Life Sciences · doi:10.1016/s0024-3205(96)00583-8 · Cited by 50 · see citing works
Molecular biology of APO E alleles in Alzheimer’s and non-Alzheimer’s dementias
Morris, C. M., Massey, H. M., Benjamin, R., Leake, A., Broadbent, C., Griffiths, M., Lamb, H., Brown, A. J., Ince, P. G., Tyrer, S. P., et al. (1996) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-6892-9_14 · Cited by 50 · see citing works
APOE is associated with age‐of‐onset, but not cognitive functioning, in late‐life depression
Butters, M. A., Sweet, R. A., Mulsant, B. H., Ilyas Kamboh, M., Pollock, B. G., Begley, A. E., Reynolds, & DeKosky, S. T. (2003) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1006 · Cited by 58 · see citing works
Self-citation

Polygenic Determinants of Alzheimer's Disease: Modulation of the Risk by α‐1‐Antichymotrypsina
DeKosky, S. T., Aston, C. E., & Kamboh, M. I. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb32595.x · Cited by 15 · see citing works
Self-citation
Apolipoprotein E and α1‐antichymotrypsin polymorphism in Alzheimer's disease
Nacmias, B., Tedde, A., Latorraca, S., Piacentini, S., Bracco, L., Amaducci, L. A., Sorbi, S., Guarnieri, B., Petruzzi, C., & Ortenzi, L. (1996) · Annals of Neurology · doi:10.1002/ana.410400420 · Cited by 36 · see citing works
Implication of α1-antichymotrypsin polymorphism in familial Alzheimer's disease
Nacmias, B., Marcon, G., Tedde, A., Forleo, P., Latorraca, S., Piacentini, S., Amaducci, L. A., & Sorbi, S. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00134-7 · Cited by 16 · see citing works
Editorial: Pragmatics and statistics in psychiatric genetics
Levinson, D. F. (1997) · American Journal of Medical Genetics · doi:10.1002/(sici)1096-8628(19970418)74:2 · Cited by 6 · see citing works
Alpha-1-Antichymotrypsin Gene Polymorphism and Risk for Sporadic Alzheimer’s Disease in a German Population
Schwab, S. G., Bagli, M., Papassotiropoulos, A., Jessen, F., Maier, W., Rao, M. L., & Heun, R. (1999) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017191 · Cited by 14 · see citing works

Authors: Kamboh, M. I., Sanghera, D. K., Ferrell, R. E., & DeKosky, S. T.
ORCID: Kamboh, M. Ilyas
Sanghera, Dharambir K.
DeKosky, Steven T.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 1995-08-01
Volume: 10
Issue: 4
Pages: 486-488
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng0895-486
OpenAlex: W2152410944
Cited by: 336
References: 26
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 7
FWCI: 26.07
Type: journal article
Language: en
Update notices: correction (1995-09-01)
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ag009202-07)
National Institute on Aging (AG 05-133, AG 07562, P50AG005133, AG09202, R01AG007562)
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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: Alzheimer's disease, APOE ε4, alpha-1-antichymotrypsin, signal peptide, genetic susceptibility, gene dosage effect, genetic modifiers, amyloid-beta, amyloid plaques
MeSH terms: Adult, Aged, Aged, 80 and over, Alleles, alpha 1-Antichymotrypsin, Alzheimer Disease, Apolipoproteins E, Base Sequence, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, Molecular Sequence Data, Polymorphism, Genetic, Risk Factors, DNA Primers, Genetic Predisposition to Disease

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A4POE*4-associated Alzheimer's disease risk is modified by α1–antichymotrypsin polymorphism

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