Effect of APOE genotype on amyloid plaque load and gray matter volume in Alzheimer disease
Abstract
OBJECTIVE: To examine the influence of the APOE genotype on levels of beta-amyloid (Abeta) plaque load and atrophy in patients with Alzheimer disease (AD) in vivo. METHODS: Thirty-two patients with moderate AD were divided into carriers and noncarriers of the epsilon4 allele. These groups were matched for age, disease duration, education, and cognitive impairment. In all subjects, [11C]PIB-PET was performed for measurement of cerebral Abeta plaque deposition and cranial MRI for the assessment of gray matter volume by voxel-based morphometry (VBM) and for correction of partial volume effects (PVE) in the PET data. Voxel-based comparisons (SPM5) were performed between patient groups and healthy control populations and completed with multiple regression analyses between imaging data and epsilon4 allele frequency. RESULTS: Compared to controls, AD-typical patterns of [11C]PIB retention and atrophy were detected in both epsilon4-positive and epsilon4-negative patient groups. In direct comparison, significantly stronger and more extended [11C]PIB uptake was found in epsilon4-positive patients in bilateral temporoparietal and frontal cortex, surviving PVE correction. VBM analysis demonstrated comparable levels of atrophy in both patient groups. Regression analyses revealed a linear association between higher epsilon4 allele frequency and stronger temporoparietal Abeta plaque deposition, independently of other confounds. No major correlation between epsilon4 allele frequency and gray matter decrease was observed. CONCLUSION: These results indicate that the epsilon4-positive APOE genotype not only represents a risk factor for Alzheimer disease (AD), but also results in higher levels of Abeta plaque deposition in epsilon4-positive patients with AD compared to age-matched epsilon4-negative patients with similar levels of cognitive impairment and brain atrophy. The potential role of Abeta plaque imaging for patient inclusion and follow-up in anti-amyloid therapy trials is strengthened by these findings.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Plaque deposition is increased with APOE4 compared with APOE2 and APOE3 in humans and transgenic mice expressing familial AD mutations.
“Plaque deposition is increased with APOE4 compared with APOE2 and APOE3 in humans and transgenic mice expressing familial AD (FAD) mutations (FAD-Tg) (2)(3)(4)(5).”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [4]
APOE4 is the primary genetic risk factor for Alzheimer disease, increasing the risk by approximately 4-fold with a single allele and 15-fold with a double allele, whereas APOE2 reduces the risk compared with APOE3.
“The primary genetic risk factor for Alzheimer disease (AD) 4 is APOE4, increasing the risk by ϳ4and 15-fold with a single or double allele, whereas APOE2 reduces the risk compared with APOE3.”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [4]
Cites
Thresholding of statistical maps in functional neuroimaging using the false discovery rate
Genovese, C. R., Lazar, N. A., & Nichols, T. (2002) · NeuroImage · doi:10.1006/nimg.2001.1037 · Cited by 4,923 · see citing works
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496 · see citing works
Imaging β-amyloid burden in aging and dementia
Rowe, C. C., Ng, S., Ackermann, U., Gong, S. J., Pike, K., Savage, G., Cowie, T. F., Dickinson, K. L., Maruff, P., Darby, D., et al. (2007) · Neurology · doi:10.1212/01.wnl.0000261919.22630.ea · Cited by 1,104 · see citing works
[ <sup>11</sup> C]PIB in a nondemented population: Potential antecedent marker of Alzheimer disease
Mintun, M. A., LaRossa, G. N., Sheline, Y. I., Dence, C. S., Lee, S. Y., Mach, R. H., Klunk, W. E., Mathis, C. A., DeKosky, S. T., & Morris, J. C. (2006) · Neurology · doi:10.1212/01.wnl.0000228230.26044.a4 · Cited by 1,036 · see citing works
Jack, C. R., Lowe, V. J., Senjem, M. L., Weigand, S. D., Kemp, B. J., Shiung, M. M., Knopman, D. S., Boeve, B. F., Klunk, W. E., Mathis, C. A., et al. (2008) · Brain · doi:10.1093/brain/awm336 · Cited by 958 · see citing works
In Vivo Mapping of Gray Matter Loss with Voxel-Based Morphometry in Mild Alzheimer's Disease
Baron, J., Chételat, G., Desgranges, B., Perchey, G., Landeau, B., Sayette, V. D. L., & Eustache, F. (2001) · NeuroImage · doi:10.1006/nimg.2001.0848 · Cited by 683 · see citing works
Berg, L., McKeel, D. W., Miller, J. P., Storandt, M., Rubin, E. H., Morris, J. C., Baty, J., Coats, M., Norton, J., Goate, A. M., et al. (1998) · Archives of Neurology · doi:10.1001/archneur.55.3.326 · Cited by 657 · see citing works
Apolipoprotein E, Dementia, and Cortical Deposition of β-Amyloid Protein
Polvikoski, T., Sulkava, R., Haltia, M., Kainulainen, K., Vuorio, A., Verkkoniemi, A., Niinistö, L., Halonen, P., & Kontula, K. (1995) · New England Journal of Medicine · doi:10.1056/nejm199511093331902 · Cited by 493 · see citing works
PET imaging of amyloid in Alzheimer's disease
Nordberg, A. K. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00853-1 · Cited by 462 · see citing works
Decreases in regional cerebral blood flow with normal aging
Martin, A. J., Friston, K. J., Colebatch, J. G., & Frackowiak, R. S. J. (1991) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1991.121 · Cited by 393 · see citing works
Arendt, T., Schindler, C., Brückner, M. K., Eschrich, K., Bigl, V., Zedlick, D., & Marcova, L. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-02-00516.1997 · Cited by 319 · see citing works
PIB is a non-specific imaging marker of amyloid-beta (A ) peptide-related cerebral amyloidosis
Lockhart, A., Lamb, J. R., Osredkar, T., Sue, L. I., Joyce, J. N., Ye, L., Libri, V., Leppert, D., & Beach, T. G. (2007) · Brain · doi:10.1093/brain/awm191 · Cited by 302 · see citing works
Shaw, P., Lerch, J. P., Pruessner, J. C., Taylor, K. N., Rose, A. B., GREENSTEIN, D. K., CLASEN, L. S., Evans, A. C., Rapoport, J. L., & Giedd, J. N. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70106-0 · Cited by 287 · see citing works
Apolipoprotein E ε4 allele, AD pathology, and the clinical expression of Alzheimer’s disease
Bennett, D. A., Wilson, R. S., Schneider, J. A., Evans, D. A., Aggarwal, N. T., Arnold, S. E., Cochran, E. J., Berry-Kravis, E., & Bienias, J. L. (2003) · Neurology · doi:10.1212/01.wnl.0000042478.08543.f7 · Cited by 282 · see citing works
Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET.
Drzezga, A. E., Grimmer, T., Riemenschneider, M., Lautenschlager, N. T., Siebner, H. R., Alexopoulus, P., Minoshima, S., Schwaiger, M., & Kurz, A. (2005) · PubMed · Cited by 277 · see citing works
Self-citationAPOE Genotype Effects on Alzheimer's Disease Onset and Epidemiology
Ashford, J. W. (2004) · Journal of Molecular Neuroscience · doi:10.1385/jmn:23:3:157 · Cited by 233 · see citing works
Impact of <i>APOE</i> genotype on neuropathologic and neurochemical markers of Alzheimer disease
Tiraboschi, P., Hansen, L. A., Masliah, E., Alford, M., Thal, L. J., & Corey-Bloom, J. (2004) · Neurology · doi:10.1212/01.wnl.0000128091.92139.0f · Cited by 226 · see citing works
β‐amyloid burden is not associated with rates of brain atrophy
Josephs, K. A., Whitwell, J. L., Ahmed, Z., Shiung, M. M., Weigand, S. D., Knopman, D. S., Boeve, B. F., Parisi, J. E., Petersen, R. C., Dickson, D. W., et al. (2007) · Annals of Neurology · doi:10.1002/ana.21223 · Cited by 224 · see citing works
Burggren, A. C., Zeineh, M., Ekstrom, A. D., Braskie, M. N., Thompson, P. M., Small, G. W., & Bookheimer, S. Y. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.03.039 · Cited by 219 · see citing works
Drzezga, A. E., Grimmer, T., Henriksen, G., Stangier, I., Perneczky, R., Diehl‐Schmid, J., Mathis, C. A., Klunk, W. E., Price, J. C., & DeKosky, S. T. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.09.020 · Cited by 202 · see citing works
Self-citationApolipoprotein E and Alzheimer's disease: molecular mechanisms and therapeutic opportunities
Cedazo-Mínguez, A. (2007) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2007.00130.x · Cited by 154 · see citing works
Apolipoprotein E ε4 and the pattern of regional brain atrophy in Alzheimer’s disease
Hashimoto, M., Yasuda, M., Tanimukai, S., Matsui, M., Hirono, N., Kazui, H., & Mori, E. (2001) · Neurology · doi:10.1212/wnl.57.8.1461 · Cited by 143 · see citing works
Beffert, U., Cohn, J. S., Petit-Turcotte, C., Tremblay, M., Aumont, N., Ramassamy, C., Davignon, J., & Poirier, J. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01894-6 · Cited by 142 · see citing works
Ziolko, S. K., Weissfeld, L. A., Klunk, W. E., Mathis, C. A., Hoge, J. A., Lopresti, B. J., DeKosky, S. T., & Price, J. C. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2006.05.063 · Cited by 119 · see citing works
Correlations Between Apolipoprotein E ε4 Gene Dose and Whole Brain Atrophy Rates
Chen, K., Reiman, E. M., Alexander, G. E., Caselli, R. J., Gerkin, R. D., Bandy, D. J., Domb, A., Osborne, D., Fox, N. C., Crum, W. R., et al. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.6.916 · Cited by 118 · see citing works
Cerebral glucose metabolism in patients with AD and different <i>APOE</i> genotypes
Drzezga, A., Riemenschneider, M., Strassner, B., Grimmer, T., Peller, M., Knoll, A., Wagenpfeil, S., Minoshima, S., Schwaiger, M., & Kurz, A. (2005) · Neurology · doi:10.1212/01.wnl.0000148478.39691.d3 · Cited by 116 · see citing works
Self-citationOhm, T., Scharnagl, H., März, W., & Bohl, J. (1999) · Acta Neuropathologica · doi:10.1007/s004010051080 · Cited by 112 · see citing works
Accelerated hippocampal atrophy in Alzheimer's disease with apolipoprotein E ε4 allele
Mori, E., Lee, K., Yasuda, M., Hashimoto, M., Kazui, H., Hirono, N., & Matsui, M. (2002) · Annals of Neurology · doi:10.1002/ana.10093 · Cited by 91 · see citing works
Apolipoprotein E, a Gene with Complex Biological Interactions in the Aging Brain
Roses, A. D. (1997) · Neurobiology of Disease · doi:10.1006/nbdi.1997.0161 · Cited by 86 · see citing works
Apolipoprotein E ϵ4 Allele, Temporal Lobe Atrophy, and White Matter Lesions in Late-Life Dementias
Barber, R., Gholkar, A. R., Scheltens, P., Ballard, C. G., McKeith, I. G., Morris, C. M., & O'Brien, J. T. (1999) · Archives of Neurology · doi:10.1001/archneur.56.8.961 · Cited by 79 · see citing works
Apolipoprotein E ε4 Allele and Whole Brain Atrophy in Late-Onset Alzheimer's Disease
Yasuda, M., Mori, E., Kitagaki, H., Yamashita, H., Hirono, N., Shimada, K., Maeda, K., & Tanaka, C. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.6.779 · Cited by 54 · see citing works
Is there a relation between APOE expression and brain amyloid load in Alzheimer's disease?
Lambert, J. (2005) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2004.048983 · Cited by 49 · see citing works
The effect of APOE ε4 allele on cerebral glucose metabolism in AD is a function of age at onset
Hirono, N., Hashimoto, M., Yasuda, M., Ishii, K., Sakamoto, S., Kazui, H., & Mori, E. (2002) · Neurology · doi:10.1212/wnl.58.5.743 · Cited by 41 · see citing works
Hämäläinen, A., Grau-Olivares, M., Tervo, S., Niskanen, E. I., Pennanen, C., Huuskonen, J., Kivipelto, M., Hänninen, T., Tapiola, M., Vanhanen, M., et al. (2008) · Neurodegenerative Diseases · doi:10.1159/000113698 · Cited by 33 · see citing works
Reiman, E. M., Chen, K., Caselli, R. J., Alexander, G. E., Bandy, D. J., Adamson, J. L., Lee, W., Cannon, A. D., Stephan, E. A., Stephan, D. A., et al. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2007.12.066 · Cited by 33 · see citing works
Apolipoprotein E polymorphism influences the cerebral metabolic pattern in Alzheimer's disease
Mielke, R., Zerres, K., Uhlhaas, S., Kessler, J., & Heiß, W.-D. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00673-9 · Cited by 29 · see citing works
Akanuma, N., Reed, L. J., Marsden, P. K., Jarosz, J., Adachi, N., Hallett, W. A., Alarcón, G., Morris, R. G., & Koutroumanidis, M. (2008) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2009.21035 · Cited by 16 · see citing works
Esler, W. P., Marshall, J. R., Stimson, E. R., Ghilardi, J. R., Vinters, H. V., Mantyh, P. W., & Maggio, J. E. (2002) · Amyloid · doi:10.3109/13506120209072439 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806 · see citing works
Clinical Neurology and Epidemiology of the Major Neurodegenerative DiseasesPreprint
Erkkinen, M. G., Kim, M., & Geschwind, M. D. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033118 · Cited by 1,152 · see citing works
Brain Imaging in Alzheimer Disease
Johnson, K. A., Fox, N. C., Sperling, R. A., & Klunk, W. E. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006213 · Cited by 875 · see citing works
<i>APOE</i> predicts amyloid‐beta but not tau Alzheimer pathology in cognitively normal aging
Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M., & Mintun, M. A. (2010) · Annals of Neurology · doi:10.1002/ana.21843 · Cited by 830 · see citing works
Barthel, H., Gertz, H., Dresel, S. H. J., Peters, O., Bartenstein, P., Büerger, K., Hiemeyer, F. J., Wittemer‐Rump, S., Seibyl, J. P., Reininger, C. B., et al. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70077-1 · Cited by 588 · see citing works
The use of PET in Alzheimer disease
Nordberg, A. K., Rinne, J. O., Kadir, A., & Långström, B. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.217 · Cited by 451 · see citing works
Sheline, Y. I., Morris, J. C., Snyder, A. Z., Price, J. L., Yan, Z., D’Angelo, G., Liu, C., Dixit, S., Benzinger, T. L. S., Fagan, A. M., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3987-10.2010 · Cited by 430 · see citing works
Drzezga, A. E., Becker, J. A., Dijk, K. R. A. V., Sreenivasan, A., Talukdar, T., Sullivan, C., Schultz, A. P., Sepulcre, J., Putcha, D., Greve, D. N., et al. (2011) · Brain · doi:10.1093/brain/awr066 · Cited by 377 · see citing works
Self-citationNeuroimaging markers for the prediction and early diagnosis of Alzheimer's disease dementia
Ewers, M., Sperling, R. A., Klunk, W. E., Weiner, M. W., & Hampel, H. J. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.05.005 · Cited by 345 · see citing works
Early-onset versus late-onset Alzheimer's disease: the case of the missing APOE ɛ4 allele
van der Flier, W. M., Pijnenburg, Y. A. L., Fox, N. C., & Scheltens, P. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70306-9 · Cited by 306 · see citing works
PET/MRI for Neurologic Applications
Catana, C., Drzezga, A. E., Heiss, W., & Rosen, B. R. (2012) · Journal of Nuclear Medicine · doi:10.2967/jnumed.112.105346 · Cited by 292 · see citing works
Self-citationChanging perspectives regarding late-life dementia
Fotuhi, M., Hachinski, V., & Whitehouse, P. J. (2009) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.175 · Cited by 291 · see citing works
Rabinovici, G. D., Furst, A. J., Alkalay, A., Racine, C. A., O’Neil, J. P., Janabi, M., Baker, S. L., Agarwal, N., Bonasera, S. J., Mormino, E. C., et al. (2010) · Brain · doi:10.1093/brain/awp326 · Cited by 280 · see citing works
APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease
Youmans, K. L., Tai, L. M., Nwabuisi-Heath, E., Jungbauer, L., Kanekiyo, T., Gan, M., Kim, J., Eimer, W. A., Estus, S., Rebeck, G. W., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.407957 · Cited by 259 · see citing works
Mild cognitive impairment: pathology and mechanisms
Mufson, E. J., Binder, L. I., Counts, S., DeKosky, S. T., deToledo‐Morrell, L., Ginsberg, S. D., Ikonomović, M. D., Perez, S. E., & Scheff, S. W. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0884-1 · Cited by 258 · see citing works
Wolk, D. A., Dickerson, B. C., Initiative, T. A. D. N., Weiner, M., Aiello, M., Aisen, P., Albert, M. S., Alexander, G., Anderson, H. S., Anderson, K., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001412107 · Cited by 248 · see citing works
Ungar, L., Altmann, A., & Greicius, M. D. (2014) · Brain Imaging and Behavior · doi:10.1007/s11682-013-9272-x · Cited by 246 · see citing works
Brown, B. M., Peiffer, J. J., Taddei, K., Lui, J. K., Laws, S. M., Gupta, V. B., Taddei, T., Ward, V. K., Rodrigues, M. A., Burnham, S., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.107 · Cited by 235 · see citing works
Beta‐amyloid deposition and the aging brain
Rodrigue, K. M., Kennedy, K. M., & Park, D. C. (2009) · Neuropsychology Review · doi:10.1007/s11065-009-9118-x · Cited by 230 · see citing works
Clinical Validation of 18 F-AZD4694, an Amyloid-β–Specific PET Radioligand
Cselényi, Z., Eriksdotter, M., Forsberg, A., Halldin, C., Julin, P., Schou, M., Johnström, P., Varnäs, K., Svensson, S., & Farde, L. (2012) · Journal of Nuclear Medicine · doi:10.2967/jnumed.111.094029 · Cited by 225 · see citing works
Emrani, S., Arain, H. A., DeMarshall, C. A., & Nuriel, T. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00712-4 · Cited by 192 · see citing works
Human APOE4 increases microglia reactivity at Aβ plaques in a mouse model of Aβ deposition
Rodriguez, G. A., Tai, L. M., LaDu, M. J., & Rebeck, G. W. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-111 · Cited by 193 · see citing works
Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo.
Rabinovici, G. D., & Jagust, W. J. (2009) · PubMed Central · doi:10.3233/ben-2009-0232 · Cited by 194 · see citing works
Cummings, J. L., Zhong, K., Kinney, J. W., Heaney, C., Moll-Tudla, J., Joshi, A., Pontecorvo, M., Devous, M., Tang, A., & Bena, J. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0173-2 · Cited by 190 · see citing works
A European multicentre PET study of fibrillar amyloid in Alzheimer’s disease
Nordberg, A., Carter, S. F., Rinne, J., Drzezga, A., Brooks, D. J., Vandenberghe, R., Perani, D., Forsberg, A., Långström, B., Scheinin, N., et al. (2013) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-012-2237-2 · Cited by 186 · see citing works
Self-citationSerrano‐Pozo, A., Qian, J., Monsell, S. E., Betensky, R. A., & Hyman, B. T. (2015) · Annals of Neurology · doi:10.1002/ana.24369 · Cited by 176 · see citing works
PET amyloid-beta imaging in preclinical Alzheimer's disease
Vlassenko, A. G., Benzinger, T. L. S., & Morris, J. C. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.11.005 · Cited by 173 · see citing works
Portelius, E., Olsson, B., Höglund, K., Cullen, N. C., Kvartsberg, H., Andréasson, U., Zetterberg, H., Sandelius, Å., Shaw, L. M. J., Lee, V. M. ‐., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1851-x · Cited by 167 · see citing works
Tai, L. M., Bilousova, T., Jungbauer, L., Roeske, S. K., Youmans, K. L., Yu, C., Poon, W. W., Cornwell, L. B., Miller, C. A., Vinters, H. V., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442103 · Cited by 165 · see citing works
Freitas, C., Mondragón-Llorca, H., & Pascual‐Leone, Á. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2011.04.001 · Cited by 164 · see citing works
Biomarkers for dementia and mild cognitive impairment in Parkinson's disease
Delgado‐Alvarado, M., Gago, B., Navalpotro‐Gómez, I., Jiménez‐Urbieta, H., & Rodríguez‐Oroz, M. (2016) · Movement Disorders · doi:10.1002/mds.26662 · Cited by 158 · see citing works
Longitudinal brain imaging in preclinical Alzheimer disease: impact of APOE ε4 genotype
Mishra, S., Blazey, T. M., Holtzman, D. M., Cruchaga, C., Su, Y., Morris, J. C., Benzinger, T. L. S., & Gordon, B. A. (2018) · Brain · doi:10.1093/brain/awy103 · Cited by 151 · see citing works
Dynamic changes in PET amyloid and FDG imaging at different stages of Alzheimer's disease
Kadir, A., Almkvist, O., Forsberg, A., Wall, A. E., Engler, H., Långström, B., & Nordberg, A. K. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.06.015 · Cited by 154 · see citing works
Epigenetics in Alzheimer’s Disease: Perspective of DNA Methylation
Qazi, T. J., Quan, Z., Mir, A., & Qing, H. (2018) · Molecular Neurobiology · doi:10.1007/s12035-016-0357-6 · Cited by 153 · see citing works
APOE Genotype and Neuroimaging Markers of Alzheimer’s Disease: Systematic Review and Meta-Analysis
Liu, Y., Yu, J.-T., Wang, H.-F., Han, P.-R., Tan, C.-C., Wang, C., Meng, X.-F., Risacher, S. L., Saykin, A. J., & Tan, L. (2015) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2014-307719 · Cited by 152 · see citing works
Koelewijn, L., Lancaster, T. M., Linden, D. E. J., Dima, D. C., Routley, B. C., Magazzini, L., Barawi, K., Brindley, L. M., Adams, R., Tansey, K. E., et al. (2019) · eLife · doi:10.7554/elife.36011 · Cited by 145 · see citing works
Tzioras, M., Davies, C., Newman, A., Jackson, R., & Spires‐Jones, T. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12529 · Cited by 147 · see citing works
The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI)
Risacher, S. L. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00011 · Cited by 143 · see citing works
White matter hyperintensities predict amyloid increase in Alzheimer's disease
Grimmer, T., Faust, M., Auer, F., Alexopoulos, P., Förstl, H., Henriksen, G., Perneczky, R., Sorg, C., Yousefi, B. H., Drzezga, A. E., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.01.016 · Cited by 139 · see citing works
Self-citationEpigenetic mechanisms in Alzheimer's disease: Implications for pathogenesis and therapy
Wang, J., Yu, J., Tan, M., Jiang, T., & Tan, L. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.05.003 · Cited by 135 · see citing works
Plasma Amyloid-β as a Biomarker in Alzheimer's Disease: The AIBL Study of Aging
Lui, J., Laws, S., Li, Q.-X., Villemagne, V., Ames, D., Brown, B., Bush, A., Ruyck, K. D., Dromey, J., Ellis, K., et al. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-090249 · Cited by 141 · see citing works
Effect of APOE ε4 genotype on amyloid-β and tau accumulation in Alzheimer’s disease
Baek, M. S., Cho, H., Lee, H. S., Lee, J., Ryu, Y. H., & Lyoo, C. H. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00710-6 · Cited by 131 · see citing works
Cerebral amyloid PET imaging in Alzheimer’s disease
Jack, C. R., Barrio, J. R., & Kepe, V. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1185-7 · Cited by 131 · see citing works
Amyloid imaging as a biomarker for cerebral β-amyloidosis and risk-prediction for Alzheimer dementia
Klunk, W. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.09.006 · Cited by 134 · see citing works
Mapping the Alzheimer’s Brain with Connectomics
Xie, T., & Yong He, A. (2012) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2011.00077 · Cited by 127 · see citing works
Barberger‐Gateau, P., Samieri, C., Féart, C., & Plourde, M. (2011) · Current Alzheimer Research · doi:10.2174/156720511796391926 · Cited by 126 · see citing works
Biomarkers in Alzheimer's disease drug development
Cummings, J. L. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.06.004 · Cited by 121 · see citing works
Zhang, S., Han, D., Tan, X., Feng, J., Guo, Y., & Ding, Y. (2012) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2011.02845.x · Cited by 121 · see citing works
Förster, S., Grimmer, T., Miederer, I., Henriksen, G., Yousefi, B. H., Graner, P., Wester, H.-J., Förstl, H., Kurz, A., Dickerson, B. C., et al. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.04.023 · Cited by 119 · see citing works
Self-citationAmyloid PET Imaging in Lewy Body Disorders
Donaghy, P. C., Thomas, A. J., & O'Brien, J. T. (2013) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2013.03.001 · Cited by 118 · see citing works
Soluble apoE/Aβ complex: mechanism and therapeutic target for APOE4-induced AD risk
Tai, L. M., Mehra, S., Shete, V., Estus, S., Rebeck, G. W., Bu, G., & LaDu, M. J. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-2 · Cited by 116 · see citing works
Differential effect of <i>APOE</i> genotype on amyloid load and glucose metabolism in AD dementia
Ossenkoppele, R., van der Flier, W. M., Zwan, M. D., Adriaanse, S. F., Boellaard, R., Windhorst, A. D., Barkhof, F., Lammertsma, A. A., Scheltens, P., & van Berckel, B. N. M. (2013) · Neurology · doi:10.1212/wnl.0b013e31827f0889 · Cited by 112 · see citing works
Devanand, D. P., Mikhno, A., Pelton, G. H., Cuasay, K., Pradhaban, G., Kumar, J. S. D., Upton, N., Lai, R. Y. K., Gunn, R. N., Libri, V., et al. (2010) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988710363715 · Cited by 107 · see citing works
Grimmer, T., Tholen, S., Yousefi, B. H., Alexopoulos, P., Förschler, A., Förstl, H., Henriksen, G., Klunk, W. E., Mathis, C. A., Perneczky, R., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.013 · Cited by 101 · see citing works
Self-citationLeoni, V. (2011) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2011.088 · Cited by 100 · see citing works
In vivo assessment of amyloid‐β deposition in nondemented very elderly subjects
Mathis, C. A., Kuller, L. H., Klunk, W. E., Snitz, B. E., Price, J. C., Weissfeld, L. A., Rosario, B. L., Lopresti, B. J., Saxton, J. A., Aizenstein, H. J., et al. (2013) · Annals of Neurology · doi:10.1002/ana.23797 · Cited by 98 · see citing works
High-Density Lipoproteins and Cerebrovascular Integrity in Alzheimer’s Disease
Stukas, S. K., Robert, J., & Wellington, C. L. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.003 · Cited by 96 · see citing works
Barthel, H., Luthardt, J., Becker, G., Patt, M., Hammerstein, E., Hartwig, K., Eggers, B., Sattler, B., Schildan, A., Hesse, S., et al. (2011) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-011-1821-1 · Cited by 98 · see citing works
Aznar, S., & Knudsen, G. M. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100390 · Cited by 93 · see citing works
Richter‐Schmidinger, T., Alexopoulos, P., Horn, M., Maus, S., Reichel, M., Rhein, C., Lewczuk, P., Sidiropoulos, C., Kneib, T., Perneczky, R., et al. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0539-8 · Cited by 93 · see citing works
Self-citationMattsson, N., Ossenkoppele, R., Smith, R. A., Strandberg, O. T., Ohlsson, T. G., Jögi, J., Palmqvist, S., Stomrud, E., & Hansson, O. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0403-x · Cited by 87 · see citing works
Apolipoprotein E ε4 modulates functional brain connectome in A lzheimer's disease
Wang, J., Wang, X., He, Y., Yu, X., Wang, H., & He, Y. (2015) · Human Brain Mapping · doi:10.1002/hbm.22740 · Cited by 87 · see citing works
The benefit of docosahexaenoic acid for the adult brain in aging and dementia
Salem, N., Vandal, M., & Calon, F. (2014) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2014.10.003 · Cited by 85 · see citing works
Amyloid load in nondemented brains correlates with APOE e4
Caselli, R. J., Walker, D. G., Sue, L. I., Sabbagh, M. N., & Beach, T. G. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.02.016 · Cited by 83 · see citing works
Fan, J., Tao, W., Li, X., Li, H., Zhang, J., Wei, D., Chen, Y., & Zhang, Z. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051177 · Cited by 83 · see citing works
Galluzzi, S., Marizzoni, M., Babiloni, C., Albani, D., Antelmi, L., Bagnoli, C., David Bartrés-faz, A., Cordone, S., Didic, M., Farotti, L., et al. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12482 · Cited by 76 · see citing works
Chiotis, K., Saint‐Aubert, L., Boccardi, M., Gietl, A. F., Picco, A., Varrone, A., Garibotto, V., Herholz, K., Nobili, F. M., Nordberg, A. K., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.07.012 · Cited by 75 · see citing works
Genetic study of multimodal imaging Alzheimer’s disease progression score implicates novel loci
Scelsi, M. A., Khan, R. R., Lorenzi, M., Christopher, L., Greicius, M. D., Schott, J. M., Ourselin, S., & Altmann, A. (2018) · Brain · doi:10.1093/brain/awy141 · Cited by 73 · see citing works
Whitehair, D. C., Sherzai, A., Emond, J. A., Raman, R., Aisen, P. S. S., Petersen, R. C., Fleisher, A., & Study, A. D. C. (2010) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2009.12.003 · Cited by 70 · see citing works
Hostage, C. A., Choudhury, K. R., Doraiswamy, P. M., Petrella, J. R., & Initiative, A. D. N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054483 · Cited by 71 · see citing works
van Vliet, D., de Vugt, M. E., Aalten, P., Bakker, C., Pijnenburg, Y. A. L., Vernooij-Dassen, M. J. F. J., Koopmans, R. T. C. M., & Verhey, F. R. J. (2012) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000342824 · Cited by 70 · see citing works
The Association−Dissociation Behavior of the ApoE Proteins: Kinetic and Equilibrium Studies
Garai, K., & Frieden, C. (2010) · Biochemistry · doi:10.1021/bi101407m · Cited by 67 · see citing works
Modifiable, Non-Modifiable, and Clinical Factors Associated with Progression of Alzheimer’s Disease
Loeffler, D. A. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201182 · Cited by 67 · see citing works
Spampinato, M. V., Rumboldt, Z., Hosker, R. J., Mintzer, J. E., & Initiative, A. D. N. (2010) · Radiology · doi:10.1148/radiol.10100307 · Cited by 67 · see citing works
Rullmann, M., Dukart, J., Hoffmann, K., Luthardt, J., Tiepolt, S., Patt, M., Gertz, H., Schroeter, M. L., Seibyl, J. P., Schulz‐Schaeffer, W., et al. (2015) · Journal of Nuclear Medicine · doi:10.2967/jnumed.115.161893 · Cited by 66 · see citing works
APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD
Manning, E. N., Barnes, J., Cash, D. M., Bartlett, J. W., Leung, K. K., Sebastien Ourselin, A., Fox, N. C., & Initiative, A. D. N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097608 · Cited by 64 · see citing works
Evidence for altered insulin receptor signaling in Alzheimer's disease
Griffith, C. M., Eid, T., Rose, G. M., & Patrylo, P. R. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.01.008 · Cited by 61 · see citing works
Neuroimaging Measures as Endophenotypes in Alzheimer′s Disease
Braskie, M. N., Ringman, J. M., & Thompson, P. M. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/490140 · Cited by 58 · see citing works
Zetzsche, T., Rujescu, D., Hardy, J., & Hampel, H. J. (2010) · Expert Review of Molecular Diagnostics · doi:10.1586/erm.10.48 · Cited by 61 · see citing works
Lehmann, M., Ghosh, P., Madison, C. A., Karydas, A., Coppola, G., O’Neil, J. P., Huang, Y., Miller, B. L., Jagust, W., & Rabinovici, G. D. (2013) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2013-305858 · Cited by 60 · see citing works
Yu, L., Lutz, M. W., Wilson, R. S., Burns, D. K., Roses, A. D., Saunders, A. M., Yang, J., Gaiteri, C., Jager, P. L. D., Barnes, L. L., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180356 · Cited by 60 · see citing works
White matter microstructure is altered in cognitively normal middle-aged APOE-ε4 homozygotes
Study, F. T. A., Operto, G., Cacciaglia, R., Grau‐Rivera, O., Falcón, C., Brugulat‐Serrat, A., Ródenas, P., Ramos, R., Morán, S., Esteller, M., et al. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0375-x · Cited by 59 · see citing works
Söderberg, L., Johannesson, M., Gkanatsiou, E., Nygren, P., Fritz, N., Zachrisson, O., Rachalski, A., Svensson, A.-S., Button, E. B., Dentoni, G., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-61691-2 · Cited by 60 · see citing works
van Vliet, D., de Vugt, M. E., Köhler, S., Aalten, P., Bakker, C., Pijnenburg, Y. A. L., Vernooij-Dassen, M. J. F. J., Koopmans, R. T. C. M., & Verhey, F. R. J. (2012) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31826cffa5 · Cited by 55 · see citing works
Recent insights into the molecular genetics of dementia
Rademakers, R., & Rovelet‐Lecrux, A. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.05.005 · Cited by 55 · see citing works
Swaminathan, S., Shen, L., Risacher, S. L., Yoder, K. K., West, J. D., Kim, S., Nho, K. T., Foroud, T., Inlow, M. H., Potkin, S. G., et al. (2011) · Brain Imaging and Behavior · doi:10.1007/s11682-011-9136-1 · Cited by 54 · see citing works
Genotator: A disease-agnostic tool for genetic annotation of disease
Wall, D. P., Perotte, R., Tong, M. Y., Jung, J.-Y., Fusaro, V. A., DeLuca, T. F., & Tonellato, P. J. (2010) · BMC Medical Genomics · doi:10.1186/1755-8794-3-50 · Cited by 52 · see citing works
Saeed, U., Mirza, S. S., MacIntosh, B. J., Herrmann, N., Keith, J. L., Ramirez, J., Nestor, S. M., Yu, Q., Knight, J., Swardfager, W., et al. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.04.005 · Cited by 52 · see citing works
Initiative, A. D. N., Liu, Y., Tan, L., Wang, H.-F., Liu, Y., Hao, X., Tan, C., Jiang, T., Liu, B., Zhang, D., et al. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9388-7 · Cited by 51 · see citing works
Murphy, K. R., Landau, S. M., Choudhury, K. R., Hostage, C. A., Shpanskaya, K. S., Sair, H. I., Petrella, J. R., Wong, T. Z., & Doraiswamy, P. M. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.04.048 · Cited by 50 · see citing works
Apolipoprotein E, amyloid-ß clearance and therapeutic opportunities in Alzheimer's disease
Kline, A. D. (2012) · Alzheimer s Research & Therapy · doi:10.1186/alzrt135 · Cited by 49 · see citing works
The potential applications of Apolipoprotein E in personalized medicine
Villeneuve, S., Brisson, D., Marchant, N. L., & Gaudet, D. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00154 · Cited by 48 · see citing works
Duarte, A. I., Santos, M. S., Oliveira, C. R., & Moreira, P. I. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.01.044 · Cited by 48 · see citing works
Kim, Y. J., Seo, S. W., Park, S. B., Yang, J., Lee, J. S., Lee, J., Jang, Y. K., Kim, S. T., Lee, K. H., Lee, J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-02046-y · Cited by 44 · see citing works
Meta-analytic Comparison Between PIB-PET and FDG-PET Results in Alzheimer’s Disease and MCI
He, W., Liu, D.-H., Radua, J., Li, G., Han, B.-J., & Sun, Z.-G. (2014) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-014-0138-7 · Cited by 50 · see citing works
Förster, S., Yousefi, B. H., Wester, H.-J., Klupp, E., Rominger, A., Förstl, H., Kurz, A., Grimmer, T., & Drzezga, A. (2012) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-012-2230-9 · Cited by 45 · see citing works
Self-citationKhan, W., Giampietro, V., Ginestet, C. E., Dell’Acqua, F., Bouls, D., Newhouse, S., Dobson, R., Banaschewski, T., Barker, G. J., Bokde, A. L. W., et al. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131841 · Cited by 44 · see citing works
Initiative, A. D. N., Arbizu, J., Prieto, E., Martínez‐Lage, P., Martí-Climent, J. M., García‐Granero, M., Lamet, I., Pástor, P., Riverol, M., Gómez‐Isla, T., et al. (2013) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-013-2458-z · Cited by 44 · see citing works
Chiesa, P., Cavedo, E., Grothe, M., Houot, M., Teipel, S., Potier, M., Habert, M., Lista, S., Dubois, B., & Hampel, H. (2019) · Radiology · doi:10.1148/radiol.2018180268 · Cited by 38 · see citing works
- Authors
- Drzezga, A., Grimmer, T., Henriksen, G., Mühlau, M., Perneczky, R., Miederer, I., Praus, C., Sorg, C., Wohlschläger, A., Riemenschneider, M., Wester, H. J., Foerstl, H., Schwaiger, M., & Kurz, A.
- Affiliations
- Technical University of Munich (DE)
- From the Departments of Nuclear Medicine (A.D., G.H., I.M., C.P., A.W., H.J.W., M.S.), Psychiatry and Psychotherapy (T.G., R.P., C.S., M.R., H.F., A.K.), Neurology (M.M.), and Neuroradiology (A.W.), Technische Universität München, Munich, Germany.
- ORCID
- Venue
- Neurology
- Published
- 2009-04-28
- Volume
- 72
- Issue
- 17
- Pages
- 1487-1494
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2050255138
- Cited by
- 248
- References
- 38
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 16 · 2021: 6 · 2020: 8 · 2019: 9 · 2018: 17 · 2017: 13 · 2016: 16 · 2015: 18 · 2014: 22 · 2013: 15 · 2012: 25
- FWCI
- 18.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- APOE ε4, Alzheimer's disease, amyloid plaques, gray matter atrophy, 11C-PiB PET, amyloid imaging, genetic risk factors, temporoparietal cortex, partial volume correction
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Aniline Compounds, Apolipoproteins E, Brain, Carbon Radioisotopes, DNA Mutational Analysis, Female, Gene Frequency, Genetic Testing, Genotype, Humans, Male, Middle Aged, Polymorphism, Genetic, Risk Factors, Thiazoles, Amyloid beta-Peptides, Genetic Predisposition to Disease, Positron-Emission Tomography, Benzothiazoles, Apolipoprotein E4, Plaque, Amyloid
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
